bluuebunny/crossref_metadata_2025 huggingface dataset:
Complete omission of second-look endoscopy after gastric endoscopic submucosal dissection in real-world practice
Authors: Funasaka Kohei , Yamada Hyuga , Horiguchi Noriyuki , Osaki Hayato , Yoshida Dai , Terada Tsuyoshi , Koyama Keishi , Okubo Masaaki , Tahara Tomomitsu , Nagasaka Mitsuo , Nakagawa Yoshihito , Shibata Tomoyuki , Ohmiya Naoki
Published: September 2022

Gastric endoscopic submucosal dissection (ESD) is increasingly performed in patients receiving antithrombotic therapy. Second-look endoscopy (SLE) has been performed empirically in several clinical settings. We investigated whether SLE omission was associated with an increased risk of postESD bleeding in all patients, including those administered antithrombotic agents.

Between July 2016 and June 2018, 229 patients were treated with a clinical pathway for gastric ESD that involved SLE on the day after ESD (SLE group). Between September 2018 and May 2020, 215 patients were treated using a clinical pathway that did not include SLE (nonSLE group). We retrospectively compared the incidence of postESD bleeding among the propensity score-matched cohorts and determined the risk factors for postESD bleeding using multivariate analysis.

The propensity score-matched cohorts showed no significant differences in the incidence of postESD bleeding between the SLE (3.2%) and nonSLE (5.1%) groups. Multivariate analysis revealed that the presence of lesions in the lower gastric body (adjusted odds ratio [OR] 2.17, 95% confidence interval [CI] 1.06–4.35, P.03) was a significant risk factor for postESD bleeding during admission, whereas resected specimen size ≥ 40 mm (adjusted OR 3.21, 95% CI 1.19–8.19, P.02) and antiplatelet therapy (adjusted OR 4.16, 95% CI 1.47–11.80, P.007) were significant risk factors after discharge.

Complete omission of SLE after gastric ESD does not increase postESD bleeding in clinical practice.
Traditional Chinese medicine therapies for patients with knee osteoarthritis: A protocol for systematic review and network meta-analysis
Authors: Wu Boyu , Yang Lei , Chen Liying , Ma Lu , Guo Yantao
Published: September 2022

Background:

Knee osteoarthritis (KOA) is a common cause of chronic musculoskeletal pain and disability as well as a socioeconomic burden on healthcare services globally. Numerous clinical trials indicated that traditional Chinese medicine (TCM) may effectively improve the clinical symptoms of KOA patients. However, the comparative efficacy and safety of different TCM therapies in patients with KOA is not yet clear. In order to evaluate the efficacy and safety of TCM for KOA, we will conduct a systematic review and network meta-analysis on the existing randomized controlled trials (RCTs).

Methods:

A systematic literature search will be conducted in PubMed, Web of Science, Embase, EBSCO, Cochrane Library, China National Knowledge Infrastructure, Wanfang, Chinese Biomedical Literature Database, and the VIP Database for Chinese Technical Periodicals up to February 2022 to identify the relevant RCTs. The primary outcomes are visual analog scale, Western Ontario and McMaster Universities Osteoarthritis Index, Lysholm score, and Lequesne index. Secondary outcomes include the total clinical effective rate and adverse events. Study quality will be evaluated using the Cochrane risk of bias tool (RoB 2.0) for RCTs. Data analysis will be performed using Stata and WinBUGS. The quality of evidence will be assessed using the Grades of Recommendations Assessment Development and Evaluation.

Results:

The results of this study will be submitted to a peer-reviewed journal for publication.

Conclusions:

This study will provide evidence-based medical evidence for the treatment of KOA with TCM therapies and offer better assistance for clinical practice.

Protocol registration number:

INPLASY202230008.
Effects of telecardiac rehabilitation on coronary heart disease: A PRISMA-compliant systematic review and meta-analysis
Authors: Jin Choo Yoo , Chang Min Cheol
Published: September 2022

Background:

We performed a meta-analysis to investigate the effectiveness of telecardiac rehabilitation compared to center-based rehabilitation on cardiorespiratory fitness, blood pressure, blood lipids, body composition, and quality of life in patients with coronary heart disease.

Methods:

We searched the Medical Literature Analysis and Retrieval System Online, Cumulative Index to Nursing and Allied Health Literature, Cochrane, Embase, and Scopus databases and retrieved studies published until October 8, 2021. Randomized controlled trials were included to evaluate cardiorespiratory fitness, blood pressure, blood lipids, body composition, and quality of life after telecardiac rehabilitation and center-based rehabilitation in patients with coronary heart disease. The criteria of the Cochrane Handbook for Systematic Reviews of Interventions were used to evaluate the methodological quality of the studies. Funnel plot analysis and Egger test were performed to confirm the publication bias.

Results:

A total of 8 studies, including 750 participants, reported the effectiveness of the telecardiac rehabilitation and center-based rehabilitation included in the analysis. Except for total cholesterol and mental quality of life (P < .05), all parameters were not significantly different between telecardiac rehabilitation and center-based rehabilitation (P > .05).

Conclusion:

Telecardiac rehabilitation was similar to the effects of center-based rehabilitation. The overall prognosis of patients with coronary heart disease can be improved by increasing patients’ participation in cardiac rehabilitation through telerehabilitation.
Postoperative radiotherapy in pIIIA-N2 non–small cell lung cancer after complete resection and adjuvant chemotherapy: A meta-analysis
Authors: Wang Shou-Feng , Mao Nai-Quan , Zhao Wen-Hua , Pan Xin-Bin
Published: September 2022

Background:

This study aimed to evaluate the effect of postoperative radiotherapy (PORT) in patients with pIIIA-N2 non–small cell lung cancer after complete resection and adjuvant chemotherapy.

Methods:

Electronic databases (PubMed, Web of Science databases, Embase, and the Cochrane Central Register of Controlled Trials) were systematically searched to extract randomized control trials comparing PORT with observation in pIIIA-N2 non–small cell lung cancer patients until October 2021. Main outcomes were disease-free survival (DFS), overall survival (OS), and local recurrence.

Results:

Three-phase 3 randomized control trials involving 902 patients were included: 455 patients in the PORT group and 447 patients in the observation group. The methodological quality of the 3 randomized control trials were high quality. The pooled analysis revealed that PORT decreased local recurrence rate (odds ratio = 0.56, 95% confidence interval [CI]: 0.40–0.76). However, PORT did not improve median DFS (hazard ratio = 0.84, 95% CI: 0.71–1.00) and OS (hazard ratio = 1.02, 95% CI: 0.68–1.52).

Conclusions:

PORT decreased the incidence of local recurrence. However, PORT did not improve DFS and OS.
The effect of lexical tone experience on English intonation perception in Mandarin-speaking cochlear-implanted children
Authors: Lu Hui-Ping , Lin Chih-Shin , Wu Che-Ming , Peng Shu-Chen , Feng I. Jung , Lin Yung-Song
Published: September 2022

To examine the effect of lexical tone experience on English intonation perception in Mandarin-speaking cochlear-implanted children during second language acquisition in Taiwan.

A retrospective cohort study.

A tertiary referred center.

Fourteen children with cochlear implant (CI) in the experimental group, and 9 normal hearing children in the control group were enrolled in this study.

Cochlear implantation and hearing rehabilitation.

Two speech recognition accuracies were examined: (1) Lexical tone recognition (4-alternative forced choice, AFC), (2) English Sentence Intonation (2AFC).

The overall accuracies for tone perception are 61.13% (standard deviation, SD = 10.84%) for CI group and 93.82% (SD = 1.80%) for normal hearing group. Tone 4 and Tone 1 were more easily to be recognized than tone 2 and tone 3 in the pediatric CI recipients (cCI) group. In English intonation perception, the overall accuracies are 61.82% (SD = 16.85%) for CI group, and 97.59% (SD = 4.73%) for normal hearing group. Significant high correlation (R = .919, P ≦ .000) between lexical tone perception and English intonation perception is noted. There is no significant difference for English intonation perception accuracies between Mandarin-speaking cCI (61.82%) and English-speaking cCI (70.13%, P = .11).

Mandarin-speaking cochlear-implanted children showed significant deficits in perception of lexical tone and English intonation relative to normal hearing children. There was no tonal language benefit in Mandarin-speaking cochlear-implanted children’s English intonation perception, compared to the English-speaking cochlear-implanted peers. For cochlear-implanted children, better lexical tone perception comes with better English intonation perception. Enhancing Mandarin prosodic perception for cochlear-implanted children may benefit their command of intonation in English.
Impact of cardiovascular comorbidity on increased neutrophil-lymphocyte ratio in pseudoexfoliation syndrome
Authors: Oh Hea Young , Lee Mee Yon , Lee Young Chun , Shin Hye-Young
Published: September 2022

Background:

The purpose of this study was to compare neutrophil-to-lymphocyte ratios (NLRs) of patients with pseudoexfoliation syndrome (PEX) according to the presence of cardiovascular disease (CVD) with those without CVD as controls.

Methods:

A total of 197 participants (97 patients with PEX and 100 participants without PEX regarded as the control group) were included in this retrospective study. The PEX group was divided into 2 subgroups, PEX with CVD (group 1) and PEX without CVD (group 2). NLRs were then compared to those of the control group.

Results:

The incidence of CVD was significantly (P = .015) higher in the PEX group than in the control group. NLR was significantly higher in the group 1 and group 2 compared with that of the control group (P = .048 and P = .002, respectively). In the PEX group, group 1 showed higher NLR than group 2 (P = .023).

Conclusion:

Although the PEX group showed a higher incidence of CVD, the NLR was higher in the PEX group regardless of cardiovascular comorbidity than that in the control group.
PD-1, PD-L1, NY-ESO-1, and MAGE-A4 expression in cutaneous angiosarcoma: A case report
Authors: Hashimoto Kazuhiko , Nishimura Shunji , Shinyashiki Yu , Ito Tomohiko , Tanaka Hiroki , Ohtani Kazuhiro , Kakinoki Ryosuke , Akagi Masao
Published: September 2022

Rationale:

The genomic alteration of cutaneous angiosarcoma (cAS) is complex. Treatment efficacy of immunotherapy for cAS remains controversial and prognosis remains poor. Herein, we report a case of cAS with programmed cell death 1, programmed cell death ligand-1, New York esophageal squamous cell carcinoma-1, and melanoma-associated antigen 4.

Patient concerns:

A 69-year-old man presented with a chief complaint of left thumb pain, with a soft tissue mass in the palmar side of the thumb. He had no past medical history. Three months prior, the man experienced the pain while scuba diving. He visited a nearby clinic, and magnetic resonance imaging revealed a soft tissue tumor on the palmar side of the thumb. He was referred to our hospital and a marginal excisional biopsy was performed.

Diagnosis:

Pathological findings revealed an angiosarcoma with high-flow serpentine vessels.

Interventions:

An excision was performed from the base of the thumb to achieve a wide margin.

Outcomes:

One year after the treatment, the patient has not experienced recurrence, metastasis, or complications.

Lessons:

Histopathology of the excised specimen was positive for programmed cell death 1, programmed cell death ligand-1, New York esophageal squamous cell carcinoma-1, and melanoma-associated antigen 4; their expression may be a therapeutic target for cAS. Combining immunotherapy with surgical treatment may be effective for cAS.
The effect of metabolic risk factors on urinary stone composition: An observational study
Authors: Kim Jae Yoon , Yu Ji Hyeong , Kang Seok Ho , Lee Jeong Gu , Cheon Jun , Kang Sung Gu
Published: September 2022

To investigate how the risk factors of metabolic diseases affect urinary stone composition, particularly uric acid (UA) stones.

Overall, 583 patients with data on urinary stone composition were retrospectively analyzed and classified into UA and nonUA stone formers according to the presence of the UA component. Various factors were compared between both groups. Participants were categorized according to age, glucose level, HbA1c level, and estimated glomerular filtration rate (eGFR) into subgroups, and the incidence of UA stone was compared.

Overall, 137 UA stone formers (23.5%) and 446 nonUA stone formers (76.5%) were included. Mean age and male-to-female ratio were higher in the UA group than in the nonUA group. The rates of diabetes mellitus (DM), hypertension, chronic kidney disease, and coronary artery disease, all of which were associated with differences in urinary stone composition, were higher in the UA group than in the nonUA group. The UA group exhibited lower mean eGFR and higher glucose and HbA1c levels. Similarly, the UA group had higher mean UA levels and predictably lower urinary pH. In subgroup analysis, higher age, glucose level, HbA1c level, and lower eGFR were associated with an increased risk of UA stone formation. In the multivariate logistic regression analysis, the UA group showed a significantly higher age (P < .001), DM frequency (P = .049), and HbA1c level (P = .032), but significantly lower eGFR than the nonUA group (P < .001).

Age and DM were independent risk factors for UA urolithiasis, implying a relationship between urinary stone composition and metabolic diseases. Additionally, renal function and HbA1c level were risk factors for UA stones.
The effectiveness of acupuncture point stimulation for the prevention of postoperative sore throat: A meta-analysis
Authors: Jau Pin-Yu , Chang Shang-Chih
Published: September 2022

Background:

Enhanced recovery pathways can be further improved for postoperative sore throat (POST) that occurs after surgery under general anesthesia. Medications have shown some effectiveness in preventing POST, but acupuncture or related techniques with better safety and lower cost can be used as an alternative or adjuvant therapy to treat perioperative symptoms by stimulating acupuncture point (acupoint). Therefore, we aimed to conduct a meta-analysis to assess whether acupoint stimulation helps patients prevent POST in adults undergoing tracheal intubation for general anesthesia.

Methods:

Publications in PubMed, the Cochrane Central Register, ScienceDirect, and ClinicalTrial.gov were surveyed from January 2000 through August 2020. Studies that compared interventions between true acupoint stimulation and no or sham acupoint stimulation were included. The primary outcomes were the incidence and severity of POST at 24h.

Results:

Four randomized control trials and 1 comparative study involving 1478 participants were included. Compared with the no or sham acupoint stimulation, the true acupoint stimulation was associated with a reduced incidence (risk ratio, 0.32; 95% confidence interval (CI), 0.18–0.55; P < .001) and decreased severity (standardized mean difference, −2.79; 95% CI, −4.59 to − 0.99; P = .002) of POST. There were no significant adverse events related to acupoint stimulation. The finding for POST was assured by subgroup, sensitivity, and trial sequential analyses.

Conclusions:

Acupoint stimulation may reduce the occurrence of POST. It can be considered as one of nonpharmacological methods to prevent POST in enhanced recovery pathways. Further rigorous studies are needed to determine the effectiveness of acupoint stimulation.
Quality of Life Among Geriatric Community Members Following the Kaohsiung Gas Explosion: A 5-Year Cross-Sectional Study
Authors: Hsu Wei-Tse , Chang Han-Yun , Lin Guijing , Lo Huei-Wen Angela , Huang Joh-Jong , Liao Che-hun , Wu Pei-Jen , Chou Frank Huang-Chin
Published: September 2022

Objective:

The aim was to conduct a follow-up study of the quality of life (QoL) and to measure lifestyle factors among the aging survivors of a petrochemical gas explosion in Taiwan 5 years after the event.

Methods:

A community-based survey with cross-sectional assessments was conducted with residents of a community who experienced a petrochemical gas explosion 5 years after the disaster. Short Form 12v2 (SF-12v2) was used to survey a representative sample of participants.

Results:

The risk factors for different QoL subscales were stressors and chronic physical illness, and the protective factors were higher income and better diet and exercise habits. The elderly participants had better diet and exercise habits than the younger participants in this survey. Aging had a negative impact on the physical QoL subscales [physical functioning (PF), bodily pain (BP), general health (GH), Physical Component Summary (PCS)] but a positive impact on psychological QoL subscales [vitality (VT), social functioning (SF), emotional problems (RE), mental health (MH), Mental Health Component Summary (MCS)].

Conclusions:

While participants’ psychiatric status had improved after 5 years, their QoL continued to be affected, especially in those with stress and physical illness. The elderly groups maintained a relatively acceptable QoL in terms of psychological aspects. Postdisaster treatment and follow-up should be addressed to a greater degree, especially in victims with mental illness or chronic illness and those with fewer socioeconomic resources.
Learning the “Science of the Art of Prescribing”: From Evidence-based Algorithms to Individualized Medicine in Psychiatric Care
Authors: King Ian , Shapiro Yakov
Published: September 2022

The purpose of this review is to highlight the limitations of the traditional diagnosis/evidence-based symptom reduction paradigm and advocate for an individualized medicine approach that incorporates psychological and relational aspects of prescribing in addition to the objective patient presentation. Potential barriers, challenges, and proposed future directions for improving education in psychological and relational aspects of prescribing are discussed. Psychological aspects of prescribing, as recently spelled out in the field of psychodynamic psychopharmacology, are generally acknowledged as important, but they do not have a well-defined position in contemporary residency training throughout North America. While residents receive in-depth exposure to diverse aspects of what to prescribe in their psychopharmacological training, and they work with patients’ subjective and relational meaning and the quality of the therapeutic alliance in their psychotherapy rotations, an integrated approach to how to prescribe is generally lacking. Despite many legitimate challenges, the authors suggest that teaching an integrated approach that incorporates objective, subjective, and relational factors in the provision of psychopharmacology and utilizing evidence-based principles of individualized care should be prioritized in both residency training and the provision of psychiatric treatment as a whole.
Forensic Mental Health Assessment as a Critical Intercept for Enhancing Mental Health Care
Authors: Holliday Ryan , Desai Alisha , Clem Matthew A. , Wortzel Hal S.
Published: September 2022

Rates of psychiatric diagnosis, medical morbidity, and suicide risk are notably high among incarcerated individuals. However, engaging these individuals in community-based health care settings can be a challenge. Among justice-involved individuals who do access services, community-based health care settings may lack available resources to effectively conduct comprehensive assessments that inform evidence-based conceptualization. We propose forensic mental health assessment (FMHA) as a critical opportunity to enhance service delivery for this at-risk population. In particular, within the scope of their role, forensic mental health evaluators are able to conduct a comprehensive review of records across health (eg, inpatient and outpatient health care settings), social (eg, homeless shelter), and correctional (eg, jail or prison) settings. Moreover, FMHA often includes specialized batteries that are able to assess and differentially diagnose myriad clinical presentations that may have overlapping symptomatology. We present 2 case vignettes to illustrate the utility of FMHA for enhancing service delivery. Finally, we conclude by noting challenges to integrating FMHA into conceptualization and necessary next steps in research and programing.
Two Cases Comparing the Presentations and Outcomes of Heroin-induced Toxic Leukoencephalopathy
Authors: HERRMANN ZACHARY , JAINI PARESH , HSU JENNIFER , RUSH A. JOHN
Published: September 2022

Heroin-induced toxic leukoencephalopathy (TLE) is an uncommon condition that presents with nonspecific and variable neuropsychiatric findings. It may result in satisfactory recovery or death. Traditionally referred to as “chasing the dragon” syndrome and associated with inhalation of pyrolyzed heroin, recent publications have reported forms of the syndrome associated with noninhaled heroin. We report 2 cases of heroin-induced TLE associated with noninhaled routes of administration and a well-documented history of opioid use disorder. The patient in the first case presented with moderate to severe symptoms. Magnetic resonance imaging of the brain revealed increased T2 and fluid-attenuated inversion recovery signals bilaterally throughout subcortical and periventricular white matter. She survived with significant cognitive issues at discharge from which she adequately recovered by 11-month follow up. The patient in the second case presented with severe symptoms. Magnetic resonance imaging of the brain showed diffuse abnormal increased T2 and fluid-attenuated inversion recovery signals in the white matter of the centrum semiovale and corona radiata. The patient died within 3 weeks of presentation. Both cases illustrate the underrecognition of the form of TLE associated with noninhaled heroin and the difficulties involved in confirming recent heroin use that likely delayed the diagnosis. Further, noninhaled heroin-induced TLE can present with specific signs and symptoms that may help clinicians delineate it from the inhaled form. Given the ongoing opioid epidemic, early and accurate recognition of this condition is of paramount importance.
The Effect of Adjunctive Probiotics on Markers of Inflammation and Oxidative Stress in Bipolar Disorder: A Double-blind, Randomized, Controlled Trial
Authors: Sabouri Salehe , Esmailzadeh Mahdi , Sadeghinejad Afsaneh , Eslami Shahrbabaki Mahin , Asadikaram Gholamreza , Nikvarz Naemeh
Published: September 2022

Background:

Bipolar disorder (BD) is a chronic psychiatric illness. Concentrations of inflammatory cytokines are increased in BD. Supplementation with probiotics has shown promising effects in reducing inflammation and producing improvement in clinical symptoms in some psychiatric disorders. Therefore, we designed a clinical trial to assess the effects of adjunctive probiotics on markers of inflammation and oxidative stress in patients with BD.

Methods:

In this 8-week, double-blind, randomized study, 38 patients suffering from BD type I were given a probiotic or placebo capsule each day. Serum levels of interleukin-6 (IL-6), as the primary outcome measure, and of interleukin-10 (IL-10), tumor necrosis factor-α, and malondialdehyde, as the secondary outcome measures, were obtained before and after the intervention.

Results:

At the end of the study, the 2 groups showed no significant or clinically meaningful differences in the serum concentrations of IL-6 [Hedge g=0.02, 95% confidence interval (CI): −0.6; 0.64, P=0.936], tumor necrosis factor-α (Hedge g=−0.2, 95% CI: −0.82; 0.42, P=0.554), IL-10 (Hedge g=−0.072, 95% CI: −0.071; 0.56, P=0.827), and malondialdehyde (Hedge g=0.27, 95% CI: −0.37; 0.91, P=0.423).

Conclusions:

This study did not find any significant or conclusive effects of probiotics supplementation on markers of inflammation and oxidative stress in patients with BD. Further studies are needed before a conclusion can be drawn about the efficacy of probiotics in the management of BD.
Association between physician's case volume in prehospital advanced trauma care and 30-day mortality: A registry-based analysis of 4,032 patients
Authors: Saviluoto Anssi , Pappinen Jukka , Kirves Hetti , Raatiniemi Lasse , Nurmi Jouni
Published: September 2022

BACKGROUND

Seriously injured patients may benefit from prehospital interventions provided by a critical care physician. The relationship between case volume and outcome has been established in trauma teams in hospitals, as well as in prehospital advanced airway management. In this study, we aimed to assess if a volume-outcome relationship exists in prehospital advanced trauma care.

METHODS

We performed a retrospective cohort study using the national helicopter emergency medical services database, including trauma patients escorted from scene to hospital by a helicopter emergency medical services physician during January 1, 2013, to August 31, 2019. In addition, similar cases during 2012 were used to determine case volumes. We performed a multivariate logistic regression analysis, with 30-day mortality as the outcome. Age, sex, Glasgow Coma Scale, shock index, mechanism of injury, time interval from alarm to the patient and duration of transport, level of receiving hospital, and physician's trauma case volume were used as covariates. On-scene times, interventions performed, and status at hospital arrival were assessed in patients who were grouped according to physician's case volume.

RESULTS

In total, 4,032 escorted trauma patients were included in the study. The median age was 40.2 (22.9–59.3) years, and 3,032 (75.2%) were male. Within 30 days, 498 (13.2%) of these patients had died. In the highest case volume group, advanced interventions were performed more often, and patients were less often hypotensive at handover. Data for multivariate analysis were available for 3,167 (78.5%) of the patients. Higher case volume was independently associated with lower mortality (odds ratio, 0.59; 95% confidence interval, 0.38–0.89).

CONCLUSION

When a prehospital physician's case volume is higher in high-risk prehospital trauma, this seems to be associated with more active practice patterns and significantly lower 30-day mortality. The quality of prehospital critical care could be increased by ensuring sufficient case volume for the providers of such care.

LEVEL OF EVIDENCE

Prognostic and Epidemiologic; Level III.
Structural studies reveal that endosomal cations promote formation of infectious CVA9 A particles, facilitating RNA and VP4 release
Authors: Domanska Aušra , Plavec Zlatka , Ruokolainen Visa , Löflund Benita , Marjomäki Varpu , Butcher Sarah J
Published: September 2022

Coxsackievirus A9, an enterovirus, is a common cause of paediatric aseptic meningitis and neonatal sepsis. During cell entry, enterovirus capsids undergo conformational changes leading to expansion, formation of large pores, externalization of VP1 N-termini and loss of the lipid factor from VP1. Factors such as receptor binding, heat, and acidic pH can trigger capsid expansion in some enteroviruses. Here we show that fatty-acid free bovine serum albumin or neutral endosomal ionic conditions can independently prime CVA9 for expansion and genome release. Our results show that CVA9 treatment with albumin or endosomal ions generates a heterogeneous population of virions, which could be physically separated by asymmetric flow field flow fractionation and computationally by cryo-EM and image processing. We report cryo-EM structures of CVA9 A-particles obtained by albumin or endosomal ion treatment and a control non-expanded virion to 3.5, 3.3 and 2.9 Å resolutions, respectively. Where albumin promotes stabile expanded virions, the endosomal ionic concentrations induce unstable CVA9 virions which easily disintegrate losing their genome. Loss of most of the VP4 molecules and exposure of negatively-charged amino acid residues in the capsid’s interior after expansion, create a repulsive viral RNA-capsid interface, aiding genome release.

Importance

Coxsackievirus A9 (CVA9) is a common cause of meningitis and neonatal sepsis. The triggers and mode of action of RNA release into the cell unusually do not require receptor interaction. Rather, a slow process in the endosome, independent of low pH is required. Here, we show by biophysical separation, cryogenic electron microscopy and image reconstruction that albumin and buffers mimicking the endosomal ion composition can separately and together expand and prime CVA9 for uncoating. Furthermore, we show in these expanded particles that VP4 is present at only ~10% of the occupancy found in the virion, VP1 is externalised and the genome is repelled by the negatively-charged, repulsive inner surface of the capsid that occurs due to the expansion. Thus, we can now link observations from cell biology of infection with the physical processes that occur in the capsid to promote genome uncoating.
Head and Neck Cancer-derived small extracellular vesicles sensitize TRPV1+ neurons to mediate cancer pain
Authors: Inyang Kufreobong E. , Evans Christine M. , Heussner Matthew , Petroff Margaret , Reimers Mark , Vermeer Paola D. , Tykocki Nathan , Folger Joseph K. , Laumet Geoffroy
Published: September 2022

Severe pain is often experienced by patients with head and neck cancer and is associated with a poor prognosis. Despite its frequency and severity, current treatments fail to adequately control cancer-associated pain, because of our lack of mechanistic understanding. Cancer-derived small extracellular vesicles (Cancer-sEVs) are well- positioned to function as mediators of communication between cancer cells and neurons. Inhibition of Cancer-sEV release attenuated pain in tumor-bearing mice. Injection of purified Cancer-sEVs is sufficient to induce pain hypersensitivity in naïve mice. Cancer-sEVs triggered calcium influx in nociceptors and inhibition or ablation of nociceptors protect against cancer pain. Interrogation of published sequencing data of human sensory neurons exposed to human Cancer-sEVs suggested a stimulation of protein translation in neurons. Induction of translation by Cancer-sEVs was validated in our mouse model and its inhibition alleviated cancer pain in mice. These findings define a role of Cancer-sEVs in cancer pain and identify several druggable targets.

Graphical abstract
Cystathionine gamma lyase overexpression enhances neovascularization through NAD-dependent mechanisms
Authors: Kiesworo Kevin , MacArthur Michael R , Kip Peter , Agius Thomas , Macabrey Diane , Lambelet Martine , Hamard Lauriane , Ozaki C.-Keith , Mitchell James R , Déglise Sebastian , Mitchell Sarah J , Allagnat Florent , Longchamp Alban
Published: September 2022

Objective

Hydrogen sulfide (H2S) is a proangiogenic gas produced primarily by the transsulfuration enzyme cystathionine-gamma-lyase (CGL). CGL-dependant H2S production is required for neovasculariation in models of peripheral arterial disease. However, the benefits of increasing endogenous CGL and its mechanism of action have yet to be elucidated.

Methods

10 weeks old male whole-body CGL overexpressing mice (CGLTg) and wild type littermates (C57BL/6J) were subjected to the hindlimb ischemia model. Functional recovery was assessed through treadmill exercise endurance testing, while ischemic leg perfusion recovery was measured by laser Doppler perfusion imaging and tissue immunohistochemistry. To examine angiogenic potential, aortic ring sprouting assay and post-natal mouse retinal vasculature development studies were performed. Lastly, comparative metabolomics, NAD+/NADH analysis, and quantitative real-time PCR were performed on WT and CGLTg gastrocnemius muscles.

Results

The restoration of blood flow upon femoral ligation occurred more rapidly in CGLTg mice. CGLTg mice were able to run further and for longer compared to WT mice. In ischemic gastrocnemius, capillary density was increased in mice overexpressing CGL. Endothelial cell sprouting was increased in aorta isolated from CGLTg mice, especially when cultured in VEGF-only media. Metabolomics analysis demonstrated an increased presence of niacinamide, a precursor of nicotinamide adenine dinucleotide (NAD+/ NADH) in the muscle of CGLTg mice. Finally, CGL overexpression and NMN supplementation improved endothelial cell migration in vitro.

Conclusions

Taken together, our results demonstrate that CGL overexpression improves the neovascularization of skeletal muscle upon hindlimb ischemia. These effects are mediated by changes in the NAD pathway, which improves endothelial cell migration.
Bayesian optimization for demographic inference
Authors: Noskova Ekaterina , Borovitskiy Viacheslav
Published: September 2022

Motivation

Inference of demographic histories of species and populations is one of the central problems in population genetics. It is usually stated as an optimization problem: find a model’s parameters that maximize a certain log-likelihood. This log-likelihood is often expensive to evaluate in terms of time and hardware resources, critically more so for larger population counts. Although genetic algorithm based solution have proven efficient for demographic inference in the past, it struggles to deal with log-likelihoods in the setting of more than three populations. Different tools are therefore needed to handle such scenarios.

Results

We introduce a new specialized optimization pipeline for demographic inference with time-consuming log-likelihood evaluations. It is based on Bayesian optimization, a prominent technique for optimizing expensive black box functions. Comparing to the existing widely used genetic algorithm solution, we demonstrate new pipeline’s superiority in time limited conditions for demographic inference with four and five populations when using log-likelihoods provided by the moments tool. Moreover, we expect this behavior to generalize just as well to other expensive-to-evaluate log-likelihood functions in the field.

Availability

The proposed method was implemented as part of the GADMA software framework and is freely and openly available on GitHub: https://github.com/ctlab/GADMA.

Contact

ekaterina.e.noskova@gmail.com, viacheslav.borovitskiy@gmail.com

Supplementary information

Supplementary materials are available as a separate document.
Reactive astrocyte derived extracellular vesicles promote functional repair post stroke
Authors: Xin Shangjing , Zhang Lucy , Phan Nhi V. , Carmichael S. Thomas , Segura Tatiana
Published: September 2022

Reactive astrocytes are both neurotoxic and pro-regenerative. Their reparative roles after injury have been demonstrated, but how they play a contributing role to regeneration remains question. Here, we investigate the use of astrocytic extracellular vesicles from primary astrocytes cultured in reactive conditions in promoting repair after ischemic stroke. Our studies show that extracellular vesicles derived from reactive astrocytes that co-express a significant number of reactive genes (155 upregulated including log2 of 9.61 forLcn2) and axonal outgrowth genes (59 upregulated including log2 of 3.49Ntn1) are necessary for improved regenerative outcomes, including axonal infiltration, vascularization, and improved behavioral recovery. Proteomic analysis of the extracellular vesicles show that astrocytes enrich pro-reparative proteins in extracellular vesicles with only 30 proteins relating to inflammatory or complement pathways loaded out of a total of 1073 proteins. Further, we show that the use of a biomaterial scaffold is necessary for the improved regeneration observed from reactive astrocyte extracellular vesicles. These studies show that reactive astrocytes use extracellular vesicles enriched with pro-repair proteins to promote recovery after injury.
Transcriptomic analysis of seed development in Paysonia auriculata (Brassicaceae) identifies genes involved in hydroxy fatty acid biosynthesis and seed maturation
Authors: Hu Hao , Swift Armond , Mauro-Herrera Margarita , Borrone James , Borja Guadalupe , Doust Andrew N.
Published: September 2022

Paysonia auriculata (Brassicaceae) produces multiple hydroxy fatty acids as major components of the seed oil. We tracked the changes in seed oil composition and gene expression during development, starting 14 days after flowers had been pollinated. Seed oil changes showed initially higher levels of saturated and unsaturated fatty acids (FAs) but little accumulation of hydroxy fatty acids (HFAs). Starting 21 days after pollination (DAP) HFA content sharply increased, and reached almost 30% at 28 DAP. Total seed oil also increased from a low of approximately 2% at 14 DAP to a high of approximately 20% by 42 DAP. We identified almost all of the fatty acid synthesis and modification genes that are known from Arabidopsis, and, in addition, a strong candidate for the hydroxylase gene that mediates the hydroxylation of fatty acids to produce valuable hydroxy fatty acids (HFAs) in this species. The gene expression network revealed is very similar to that of the emerging oil crop, Physaria fendleri, in the sister genus to Paysonia. Phylogenetic analyses indicate the hydroxylase enzyme, FAH12, evolved only once in Paysonia and Physaria, and that the enzyme is closely related to FAD2 enzymes. Phylogenetic analyses of FAD2 and FAH12 in the Brassicaceae and outgroup genera suggest that the branch leading to the hydroxylase clade of Paysonia and Physaria is under relaxed selection, compared with the strong purifying selection found across the FAD2 lineages.
Early suppression of excitability in subcortical band heterotopia modifies epileptogenesis in rats
Authors: Hardy Delphine , Buhler Emmanuelle , Suchkov Dmitrii , Vinck Antonin , Fortoul Aurélien , Watrin Françoise , Represa Alfonso , Minlebaev Marat , Manent Jean-Bernard
Published: September 2022

Malformations of cortical development represent a major cause of epilepsy in childhood. However, the pathological substrate and dynamic changes leading to the development and progression of epilepsy remain unclear. Here, we characterized an etiology-relevant rat model of subcortical band heterotopia (SBH), a diffuse type of cortical malformation associated with drug-resistant seizures in humans. We used longitudinal electrographic recordings to monitor the age-dependent evolution of epileptiform discharges during the course of epileptogenesis in this model. We found both quantitative and qualitative age-related changes in seizures properties and patterns, accompanying a gradual progression towards a fully developed seizure pattern seen in adulthood. We also dissected the relative contribution of the band heterotopia and the overlying cortex to the development and age-dependent progression of epilepsy using timed and spatially targeted manipulation of neuronal excitability. We found that an early suppression of neuronal excitability in SBH slows down epileptogenesis in juvenile rats, whereas epileptogenesis is paradoxically exacerbated when excitability is suppressed in the overlying cortex. However, in rats with active epilepsy, similar manipulations of excitability have no effect on chronic spontaneous seizures. Together, our data support the notion that complex developmental alterations occurring in both the SBH and the overlying cortex concur to creating pathogenic circuits prone to generate seizures. Our study also suggests that early and targeted interventions could potentially influence the course of these altered developmental trajectories, and favorably modify epileptogenesis in malformations of cortical development.

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Cross-tissue multiomics studies reveal gut-brain interactions mediating the effect of Akkermansia muciniphila in counteracting fructose-induced obesity
Authors: Ha Sung Min , Ahn In-Sook , Kowal-safron Thomas , Yoon Justin , Diamante Graciel , Cely Ingrid , Zhang Guanglin , Wang Susana , Yang Xia
Published: September 2022

The gut bacterium Akkermansia muciniphila (A. muciniphila) has been implicated in anti-obesity effects, but a systems level understanding of the molecular mechanisms is lacking. We carried out multiomics studies to investigate the molecular cascades mediating the anti-obesity effect of A. muciniphila in a fructose-induced obesity mouse model. We found that A. muciniphila colonization triggered significant shifts in gut microbiota composition, gut and plasma metabolites, and gene expression in hypothalamic neurons. Multiomics integration and network analysis prioritized the metabolite oleoyl-ethanolamide (OEA) in the gut and circulation as a regulator of gut-brain interactions that underlie the A. muciniphila anti-obesity effect. Oral administration of OEA counteracted the fructose-induced obesity through the regulation of hypothalamic anorexigenic neuropeptides such as oxytocin and arginine vasopressin. Our multiomics investigation and experimental validation elucidates the molecular regulators and pathways involved in the communication between A. muciniphila in the gut and hypothalamic neurons that counter fructose-induced obesity.
No evidence for associations between brood size, gut microbiome diversity and survival in great tit (Parus major) nestlings
Authors: Liukkonen M. , Hukkanen M. , Cossin-Sevrin N. , Stier A. , Vesterinen E. , Grond K. , Ruuskanen S.
Published: September 2022

Background

The gut microbiome forms at an early stage, yet data on the environmental factors influencing the development of wild avian microbiomes is limited. As the gut microbiome is a vital part of organismal health, it is important to understand how it may connect to host performance. The early studies with wild gut microbiome have shown that the rearing environment may be of importance in gut microbiome formation, yet the results vary across taxa, and the effects of specific environmental factors have not been characterized. Here, wild great tit (Parus major) broods were manipulated to either reduce or enlarge the original brood soon after hatching. We investigated if brood size was associated with nestling bacterial gut microbiome, and whether gut microbiome diversity predicted survival. Fecal samples were collected at mid-nestling stage and sequenced with the 16S rRNA gene amplicon sequencing, and nestling growth and survival were measured.

Results

Gut microbiome diversity showed high variation between individuals, but this variation was not significantly explained by brood size or body mass. Additionally, we did not find a significant effect of brood size on body mass or gut microbiome composition. We also demonstrated that early handling had no impact on nestling performance or gut microbiome. Furthermore, we found no significant association between gut microbiome diversity and short-term (survival to fledging) or mid-term (apparent juvenile) survival.

Conclusions

We found no clear association between early-life environment, offspring condition and gut microbiome. This suggests that brood size is not a significantly contributing factor to great tit nestling condition, and that other environmental and genetic factors may be more strongly linked to offspring condition and gut microbiome. Future studies should expand into other early-life environmental factors e.g., diet composition and quality, and parental influences.
A three-strain synthetic community model whose rapid response to antagonism allows the study of higher-order dynamics and emergent properties in minutes
Authors: Aguilar-Salinas Bernardo , Olmedo-Álvarez Gabriela
Published: September 2022

A fundamental question in the assembly of microbial communities is how complex systems arise from a few components. Synthetic communities allow addressing the dynamics and mechanisms of complex microbial interactions. Most studies on microbial interactions are done in lapses of hours and even days, but microbes must be able to sense danger in seconds. We assembled a three-strain synthetic community from the phylum Bacillota that, based on previously evaluated paired interactions, appear to have different ecological roles: resistant (R), antagonists (A), and sensitive (S). The BARS synthetic community (Bacillota A + S + R) reproduces features of complex communities and exhibits higher-order interaction dynamics. The majority of the S strain population, Sutclifiella horikoshii 20a, dies within 5 min in a paired interaction with A strain, Bacillus pumilus 145. An emergent property appears upon adding the third interactor, as antagonism of strain A over S is not observed in the presence of the R strain, Bacillus cereus 111. After the first five min a change of state of the cells is observed, as the surviving population of the S strain seemed to have acquired tolerance to A. In summary, our model allows the study of the assembly dynamics of a three-species community and to evaluate the immediate outcome within a 30 min frame. The BARS has features of a complex system where the paired interactions do not predict the community dynamics. The model is amenable to mechanistic dissection and to modeling how the parts integrate to achieve collective properties.

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IMPORTANCE

Microbial communities are of utmost importance, given their roles in health, agriculture, and all biogeochemical cycles on Earth. Synthetic ecology studies communities by reducing the number of variables. Microbial interactions are usually evaluated in hours or days, however, upon a first encounter, bacteria must respond in minutes, particularly when competition involves killing of neighboring cells. We generated a synthetic community of three species that allows the study of community dynamics in a 30 min frame. We denominated our model BARS as it comprises Bacillota strains that in paired interactions are Antagonist, Resistant, or Sensitive. Even though in paired interaction the antagonist kills the sensitive strain, in a triple interaction, the resistant strain provides stability to the community by neutralizing the antagonism. Therefore, BARS is a rapid response model with features of a complex system where the paired interactions do not predict the community dynamics and exhibit emergent properties.
The piRNA clustertorimochiis an expanding transposon in cultured silkworm cells
Authors: Shoji Keisuke , Umemura Yusuke , Tomari Yukihide
Published: September 2022

PIWI proteins and PIWI-interacting RNAs (piRNAs) play a central role in repressing transposable elements in animal germ cells. It is thought that piRNAs are mainly produced from discrete genomic loci named piRNA clusters, which often contain many “dead” transposon remnants from past invasions and have heterochromatic features. In the genome of silkworm ovary-derived cultured cells called BmN4, a well-established model for piRNA research,torimochiwas previously annotated as a unique and specialized genomic region that can capture transgenes and produce new piRNAs bearing a trans-silencing activity. However, the sequence identity oftorimochihas remained elusive. Here, we carefully characterizedtorimochiby utilizing the updated silkworm genome sequence and the long-read sequencer MinION. We found thattorimochiis in fact a full-length gypsy-like LTR retrotransposon, which is exceptionally active and has massively expanded its copy number in BmN4 cells. Many copies oftorimochiin BmN4 cells have features of open chromatin and the ability to produce piRNAs. Therefore,torimochimay represent a young, growing piRNA cluster, which is still “alive” and active in transposition yet capable of trapping other transposable elements to producede novopiRNAs. (185 words)