bluuebunny/crossref_metadata_2025 huggingface dataset:
Megalin is involved in angiotensinogen-induced, angiotensin II-mediated ERK1/2 signaling to activate Na+-H+ exchanger 3 in proximal tubules
Authors: Goto Sawako , Yoshida Yutaka , Hosojima Michihiro , Kuwahara Shoji , Kabasawa Hideyuki , Aoki Hiroyuki , Iida Tomomichi , Sawada Ryuhei , Ugamura Daisuke , Yoshizawa Yuta , Takemoto Kazuya , Komochi Koichi , Kobayashi Ryota , Kaseda Ryohei , Yaoita Eishin , Nagatoishi Satoru , Narita Ichiei , Tsumoto Kouhei , Saito Akihiko
Published: September 2023

Background:

Kidney angiotensin (Ang) II is produced mainly from liver-derived, glomerular-filtered angiotensinogen (AGT). Podocyte injury has been reported to increase the kidney Ang II content and induce Na+ retention depending on the function of megalin, a proximal tubular endocytosis receptor. However, how megalin regulates the renal content and action of Ang II remains elusive.

Methods:

We used a mass spectrometry-based, parallel reaction-monitoring assay to quantitate Ang II in plasma, urine, and kidney homogenate of kidney-specific conditional megalin knockout (MegKO) and control (Ctl) mice. We also evaluated the pathophysiological changes in both mouse genotypes under the basal condition and under the condition of increased glomerular filtration of AGT induced by administration of recombinant mouse AGT (rec-mAGT).

Results:

Under the basal condition, plasma and kidney Ang II levels were comparable in the two mouse groups. Ang II was detected abundantly in fresh spot urine in conditional MegKO mice. Megalin was also found to mediate the uptake of intravenously administered fluorescent Ang II by PTECs. Administration of rec-mAGT increased kidney Ang II, exerted renal extracellular signal-regulated kinase 1/2 (ERK1/2) signaling, activated proximal tubular Na+-H+ exchanger 3 (NHE3), and decreased urinary Na+ excretion in Ctl mice, whereas these changes were suppressed but urinary Ang II was increased in conditional MegKO mice.

Conclusion:

Increased glomerular filtration of AGT is likely to augment Ang II production in the proximal tubular lumen. Thus, megalin-dependent Ang II uptake should be involved in the ERK1/2 signaling that activates proximal tubular NHE3 in vivo, thereby causing Na+ retention.
A Systematic Literature Review of Disease Progression Reported in RPGR-associated X-linked Retinitis Pigmentosa
Authors: Lam Byron L. , Scholl Hendrik P. N. , Doub Daneal , Sperling Marvin , Hashim Mahmoud , Li Nan
Published: September 2023

Purpose:

RPGR-associated X-linked retinitis pigmentosa (RPGR-XLRP) is a rare and severe form of retinitis pigmentosa (RP) resulting in progressive visual impairment; however, disease progression data are limited. A systematic literature review was conducted to assess available data on disease progression in RPGR-XLRP.

Methods:

PubMed, EMBASE, and select congress abstracts were evaluated through June 2022. Eligible studies included results specific to RPGR-XLRP or populations with ≥80% of RP patients carrying disease-causing RPGR variants. Endpoints of interest included visual acuity (VA), visual field (VF), ellipsoid zone width (EZW), progression to blindness, and patient-reported outcomes (PROs).

Results:

Fourteen studies met ≥1 endpoint of interest. Progressive declines in VA, VF, and EZW were reported across studies. Nearly all publications reported annual declines in VA (3.5%-8.2%). Annual VF declines ranged from 4.2% to 13.3%. Changes in retinal structure were also observed (EZW changes: –177 to –830 μm/y). Most studies measured blindness using VA; VF-based definitions resulted in blindness by age ∼25 years. PRO data were limited.

Conclusion:

Published evidence shows that patients with RPGR-XLRP experience progressive decline in VA, VF, and EZW, eventually resulting in blindness. Additional longitudinal data with standardized endpoints and expanded collection of PROs are needed to assess visual decline in RPGR-XLRP.
PREFOVEAL ADHERENT HEAVY SILICONE OIL AFTER VITRECTOMY: INCIDENCE, CLINICAL FEATURES, AND RISK FACTORS
Authors: Akyol Mehmet , Zewar Ahmed , Lochhead Jonathan
Published: September 2023

Purpose:

The purpose of this study was to study the optical coherence tomography (OCT) and clinical features of all patients presenting with prefoveal “sticky” heavy silicone oil (HSO) after vitreoretinal surgery and subsequent oil removal.

Methods:

A retrospective review of all consecutive patients who underwent vitreoretinal surgery with HSO tamponade over 12 years was performed. All OCT scans were reviewed after HSO removal to determine features consistent with residual prefoveal oil deposits. A detailed analysis was performed to investigate potential clinical features and possible associations.

Results:

Seven cases of prefoveal HSO (pfHSO) were identified from a total of 51 consecutive cases (13.7%). All cases of pfHSO had a tamponade duration exceeding 3 months. The mean tamponade duration in the pfHSO group was 7.8 (3.5–21) months compared with 4.6 (1–9) months in the unaffected group. The use of mixed HSO compared with HSO increases the risk of pfHSO changes (P = 0.024).

Conclusion:

In summary, 7 novel cases of sticky pfHSO remnants with variable OCT dimensions were identified, which could have an impact on the visual prognosis. Removal of pfHSO is extremely challenging and may not always be possible. There were no pfHSO patients identified below 3 months of tamponade duration.
Ophthalmologic Findings in Pediatric Erdheim-Chester Disease: A Literature Review With a Novel Case Report
Authors: Yeager Lauren B. , Grimes Joseph M. , Dal Col Alexis K. , Shah Nirav V. , Bogomolny Dmitry , Debelenko Larisa , Marr Brian P.
Published: September 2023

Purpose:

The authors aim to describe the ophthalmologic manifestations of pediatric Erdheim-Chester disease (ECD).

Methods:

The authors describe a novel case of ECD presenting as isolated bilateral proptosis in a child and provide a comprehensive review of the documented pediatric cases to observe overall trends and ophthalmic manifestations of disease. Twenty pediatric cases were identified in the literature.

Results:

The mean age at presentation was 9.6 years (1.8–17 years) with a mean time of symptom presentation to diagnosis of 1.6 years (0–6 years). Nine patients (45%) had ophthalmic involvement at diagnosis, 4 who presented with ophthalmic complaints: 3 with observable proptosis and 1 with diplopia. Other ophthalmic abnormalities included eyelid findings of a maculopapular rash with central atrophy on the eyelids and bilateral xanthelasmas, neuro-ophthalmologic findings of a right hemifacial palsy accompanied by bilateral optic atrophy and diplopia, and imaging findings of orbital bone and enhancing chiasmal lesions. No intraocular involvement was described, and visual acuity was not reported in most cases.

Conclusions:

Ophthalmic involvement occurs in almost half of documented pediatric cases. Typically presenting with other symptoms, the case highlights that isolated exophthalmos may be the only clinical sign, and ECD should be included in the differential diagnosis of bilateral exophthalmos in children. Ophthalmologists may be the first to evaluate these patients, and a high index of suspicion and an understanding of the varied clinical, radiographic, pathologic, and molecular findings are critical for prompt diagnosis and treatment of this unusual disease.
Obstructive sleep apnea in the patient with atrial fibrillation: current knowledge and remaining uncertainties
Authors: Lyons Owen D.
Published: September 2023

Purpose of review

Obstructive sleep apnea (OSA) is highly prevalent in patients with atrial fibrillation and plays a causal role for OSA in the pathogenesis of atrial fibrillation. The presence of OSA in atrial fibrillation is associated with increased symptom burden and increased risk of hospitalizations. Furthermore, untreated OSA is associated with an increased risk of atrial fibrillation recurrence post ablation or cardioversion, and observational studies suggest that continuous positive airway pressure (CPAP) therapy can attenuate this risk. This review describes our current understanding of the relationship between OSA and atrial fibrillation with an emphasis on emerging evidence.

Recent findings

Recent studies have identified novel screening questionnaires, which may be superior to traditional questionnaires in identifying OSA in atrial fibrillation populations. Significant night-to-night variability in OSA severity has been shown in atrial fibrillation patients, which has implications for diagnostic testing. While several small, randomized control trials (RCTs) have not shown CPAP therapy to be effective in reducing atrial fibrillation burden, one RCT did show CPAP can attenuate the atrial substrate with implications for long-term outcomes.

Further RCTs, appropriately powered, and focused on well defined cohorts, are required to guide management decisions regarding screening and treatment of OSA in atrial fibrillation populations.
Early versus delayed laparoscopic cholecystectomy after endoscopic retrograde cholangiopancreatography: A meta-analysis
Authors: Qi Sheng , Xu Jie , Yan Chao , He Yanan , Chen Yao
Published: September 2023

Purposes:

Patients with cholecysto- and choledocholithiasis usually undergo endoscopic retrograde cholangiopancreatography (ERCP)/-endoscopic sphincterotomy followed by laparoscopic cholecystectomy (LC). However, differences in the timing of LC after the ERCP may alter the post-operative outcomes. The aim of this study was to compare the effect of early (≤3 days) or delayed LC (>3 days) following ERCP on the post-operative outcomes.

Methods:

A comprehensive search of the 3 databases PubMed, EMBASE and the Cochrane Library was performed. Articles related to LC at different time-points after ERCP were retrieved. Dichotomous and continuous outcomes were analyzed by risk ratio (RR) and mean difference, and RevMan was used to analyze each group.

Results:

A total of 7 studies, including 5 randomized controlled studies and 2 retrospective studies, involved a total of 711 patients. There were 332 patients in early LC group and 379 in delayed LC group. The conversion rate was lower in the early LC group compared to the delayed LC group (RR 0.38, 95% confident interval 0.19 to 0.74,P= .005, I2= 0%). Early LC resulted in a shorter operation time (RR −6.2, 95% CI −27.2 to −5.2,P= .004, I2= 97%) and fewer complications (RR 0.48, 95% CI 0.29 to 0.79,P= .004, I2= 17%). Subgroup analysis found that there were no significant differences in the conversion rate (RR 0.61, 95% CI 0.25 to 1.45,P= .26, I2= 0%) or complications between the early LC group and the delayed group who underwent LC after 1 month.

Conclusion:

Early LC after ERCP is the preferred treatment for patients with concurrent cholecysto- and choledocholithiasis due to improved clinical outcomes as compared to those who undergo delayed LC.
The fibrinogen-albumin ratio as a novel prognostic factor for elderly patients with osteosarcoma
Authors: Fu Yang , Yu Yang , Zhou Yi , Li Tong , Xie Yizhou , Wang Yehui , Ran Qiang , Chen Yiming , Fan Xiaohong
Published: September 2023

To analyze the prognostic value of fibrinogen-albumin ratio (FAR) in predicting the overall survival in elderly osteosarcoma patients. One hundred nineteen elderly osteosarcoma patients (> 40 years old) from 2 centers were retrospectively reviewed and analyzed. The cutoff values of the biomarker were calculated via receiver operating characteristic curves, and the cohort was divided into high FAR group and low FAR group. The association between the FAR and clinical-pathological parameters was analyzed. And the prognosis of elderly osteosarcoma patients and the potential risk factors were analyzed using Kaplan–Meier method and Cox proportional hazards model. Finally, a clinical nomogram was constructed, and its predictive capacity was verified. According to receiver operating characteristic results, the cutoff value for FAR was 0.098, and the enrolled patients were divided into the low FAR group and high FAR group. The FAR was significantly correlated with several clinical-pathological characteristics, including age, tumor size, tumor stage, recurrence, and metastasis. Moreover, the multivariate Cox analyses results showed that the FAR, pathological fracture, and metastasis were independent risk factors for overall survival in elderly osteosarcoma patients. The predictive nomogram was subsequently constructed, representing satisfactory predictive performance for prognosis in elderly patients with osteosarcoma. The FAR value is a promising indicator for elderly osteosarcoma patients, which is correlated with the various clinical characteristics and prognosis. A clinical nomogram integrating FAR and other clinical indicators is a convenient and available tool to assess the prognosis and manage the individualized and precise treatment of elderly patients with osteosarcoma.
Dosimetric performance evaluation of the Halcyon treatment platform for stereotactic radiotherapy: A pooled study
Authors: Huang Yangyang , Liu Zongwen
Published: September 2023

With the advancement of radiotherapy equipment, stereotactic radiotherapy (SRT) has been increasingly used. Among the many radiotherapy devices, Halcyon shows promising applications. This article reviews the dosimetric performance such as plan quality, plan complexity, and gamma passing rates of SRT plans with Halcyon to determine the effectiveness and safety of Halcyon SRT plans. This article retrieved the last 5 years of PubMed studies on the effectiveness and safety of the Halcyon SRT plans. Two authors independently reviewed the titles and abstracts to decide whether to include the studies. A search was conducted to identify publications relevant to evaluating the dosimetric performance of SRT plans on Halcyon using the key strings Halcyon, stereotactic radiosurgery, SRT, stereotactic body radiotherapy, and stereotactic ablative radiotherapy. A total of 18 eligible publications were retrieved. Compared to SRT plans on the TrueBeam, the Halcyon has advantages in terms of plan quality, plan complexity, and gamma passing rates. The high treatment speed of SRT plans on the Halcyon is impressive, while the results of its plan evaluation are also encouraging. As a result, Halcyon offers a new option for busy radiotherapy units while significantly improving patient comfort in treatment. For more accurate results, additional relevant publications will need to be followed up in subsequent studies.
Exploring the mechanism of Semen Strychni in treating amyotrophic lateral sclerosis based on network pharmacology
Authors: Tang Xiaohui , Zhan Yingshi , Yang Biying , Du Baoxin , Huang Jingyan
Published: September 2023

Semen Strychni (SS), known as an agonist of central nervous system, is a traditional herb widely used in treating amyotrophic lateral sclerosis (ALS) in small doses to relieve muscle weakness and improve muscle strength. However, the potential mechanisms and the main components of SS in treating ALS remain unclear. To explore the underlying mechanism of SS in treating ALS based on network pharmacology and molecular docking. The active components of SS were obtained using TCMSP, Herb, ETCM, and BATMAN-TCM. The targets of SS were gained from PharmMapper. The targets of ALS were searched on Genecards, Drugbank, DisGeNET, OMIM, TTD and GEO database. After obtaining the coincidence targets, we submitted them to the STRING database to build a protein-protein interaction network. Gene ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis were performed subsequently. The active components and targets were further investigated using molecular docking technology. 395 targets of SS and 1925 targets of ALS were obtained with 125 common targets. The protein-protein interaction analysis indicated that SRC, AKT1, MAPK1, EGFR, and HSP90AA1 received the higher degree value and were considered the central genes. The Ras, PI3K-Akt, and MAPK signaling pathway could be involved in the treatment of ALS. Brucine-N-oxide obtained the lowest binding energy in molecular docking. This study explored the mechanism of SS in the treatment of ALS and provides a new perspective for future study. However, further experimental studies are needed to validate the therapeutic effect.
Long-term cognitive dysfunction after the COVID-19 pandemic: a narrative review
Authors: Shariff Sanobar , Uwishema Olivier , Mizero Jocelyn , Devi Thambi Vimala , Nazir Abubakar , Mahmoud Ashraf , Kaushik Ikshwaki , Khayat Saadeddine , Yusif Maigoro Abdulkadir , Awde Sara , Al Maaz Zeina , Alwan Iktimal , Hijazi Mahdi , Wellington Jack , Soojin Lee
Published: September 2023

Introduction:

SARS-CoV-2, the virus responsible for the COVID-19 pandemic, has brought a conglomerate of novel chronic disabling conditions described as ‘Long COVID/Post-COVID-19 Syndrome’. Recent evidence suggests that the multifaceted nature of this syndrome results in both pulmonary and extrapulmonary sequelae,chronic dyspnoea, persistent fatigue, and cognitive dysfunction being the most common, debilitating symptoms. Several mechanisms engender or exacerbate cognitive impairment, including central nervous system and extra-central nervous system causes, although the exact mechanism remains unclear. Both hospitalized and non-hospitalized patients may suffer varying degrees of cognitive impairment, ranging from fatigue and brain fog to prolonged deficits in memory and attention, detrimental to the quality-of-life years post-recovery. The aim of this review is to understand the underlying mechanisms, associations, and attempts for prevention with early intervention of long-term cognitive impairment post-COVID-19.

Methodology:

A systematic search was conducted through multiple databases such as Medline, National Library of Medicine, Ovid, Scopus database to retrieve all the articles on the long-term sequalae of cognitive dysfunction after SARS-CoV-2 infection. The inclusion criteria included all articles pertinent to this specific topic and exclusion criteria subtracted studies pertaining to other aetiologies of cognitive dysfunction. This search was carefully screened for duplicates and the relevant information was extracted and analysed.

Results/discussion:

To date, the exact pathogenesis, and underlying mechanisms behind cognitive dysfunction in COVID-19, remain unclear, hindering the development of adequate management strategies. However, the proposed mechanisms suggested by various studies include direct damage to the blood-brain barrier, systemic inflammation, prolonged hypoxia, and extended intensive care admissions. However, no clear-cut guidelines for management are apparent.

Conclusion:

This review of the COVID-19 pandemic has elucidated a new global challenge which is affecting individuals’ quality of life by inducing long-term impaired cognitive function. The authors have found that comprehensive evaluations and interventions are crucial to address the cognitive sequelae in all COVID-19 patients, especially in patients with pre-existing cognitive impairment. Nevertheless, the authors recommend further research for the development of relevant, timely neurocognitive assessments and treatment plans.
Calciphylaxis during the course of psoriatic arthritis patient. Is it coincidence? A case report
Authors: Khalayli Naram , Hodifa Yara , Hodaifa Amr , Alsamarrai Omar , Kudsi Maysoun
Published: September 2023

Introduction and importance:

Calciphylaxis manifests clinically by skin ischemia and necrosis and histologically by calcification of dermal arterioles. Usually, it occurs in patients with end-stage renal disease on dialysis or in patients who had a kidney transplant. Here, the authors present a case of calciphylaxis occurring in a patient with psoriasis and psoriatic arthritis.

Case presentation:

A 66-year-old Syrian male with a history of psoriatic arthritis presented for evaluation of 2-month nonpainful ulcers on his feet and hands that were treated with warfarin. Biopsies confirmed the diagnosis of calciphylaxis. The patient received sodium thiosulfate, zoledronic acid, intralesional sodium thiosulfate injections, and an intravenous infusion of vitamin K with dramatic improvement. At the 3-month follow-up, his wounds had been completely remitted.

Discussion:

Nonuremic calciphylaxis occurs in many cases, like vitamin D administration, vitamin K antagonists’ administration, chronic inflammation, and others. The association between calciphylaxis and psoriasis was reported only in four cases in the literature; meanwhile, this was the first case that described calciphylaxis in the setting of psoriatic arthritis.

Conclusion:

A suspicion of calciphylaxis should be maintained in patients with underlying inflammatory mechanism diseases.
Medications Cost Resources
Authors: Bristow Alice S. , Jones Leslie M. , Bruce Rachael T. , Grant Joan S.
Published: September 2023

High cost of prescription drugs is a common reason why patients stop taking medications, or don't fill a prescription. There are cost savings plans available, but these resources vary by eligibility criteria, and each has advantages and disadvantages. The article reviews some of the available cost saving options.
Visualization of Thromboinflammation by 18F-DPA-714 PET in a Stroke Patient
Authors: Lin Qianqian , Wang Youliang , Zhao Wenlong , Yao Shaobo
Published: September 2023

A 44-year-old man who presented with progressive right limb weakness was diagnosed with ischemic stroke. He was referred for 18F-DPA-714 PET/CT for evaluation of the disease. 18F-DPA-714 PET/CT showed increased uptake of the intracranial thrombus. This DPA-714–avid thrombus highly suggested the involvement of immune cells in the extension of the clot resulting in neurological deterioration. This present case suggested that 18F-DPA-714 PET might be a promising tracer in visualizing thromboinflammation in vivo.
How should tranexamic acid be administered in haemorrhagic shock? - continuous serum concentration measurements in a swine model
Authors: Lynghaug Trine , Bakke Håkon Kvåle , Fuskevåg Ole Martin , Nielsen Erik Waage , Dietrichs Erik Sveberg
Published: September 2023

Background

Tranexamic acid (TXA) reduces mortality in trauma patients. Intramuscular (i.m.) administration could be advantageous in low-resource and military settings. Achieving the same serum concentration as i.v. administration is important to achieve equal mortality reduction. Therefore, we aimed to investigate whether dividing an i.m. dose of TXA between two injection sites, and whether an increase in dose, would lead to serum concentrations comparable to those achieved by i.v. administration.

Methods

Norwegian landrace pigs (n = 29) from a course in haemostatic emergency surgery were given tranexamic acid 1 h after start of surgery. Blood samples were drawn at 0, 5,10, 15, 20, 25, 35, 45, 60 and 85 min. The samples were centrifuged and serum TXA concentrations quantified with liquid chromatography–tandem mass spectrometry (LC–MS/MS). The use of two injection sites was compared to distributing the dose on one injection site, and a dose of 15 mg/kg was compared to a dose of 30 mg/kg. All i.m. groups were compared to i.v. administration.

Results

The groups were in a similar degree of shock. Increasing the i.m. dose from the standard of 15 mg/kg to 30 mg/kg resulted in significantly higher serum concentrations of TXA, comparable to those achieved by i.v. administration. Distributing the i.m. dose on two injection sites did not affect drug-uptake, as shown by equal serum concentrations.

Conclusions

For i.m. administration of TXA, 30 mg/kg should be the standard dose. With a short delay, i.m. administration will provide equal serum concentrations as i.v. administration, above what is considered necessary to inhibit fibrinolysis.
Differential Impact of the UNOS Simultaneous Liver-kidney Transplant Policy Change Among Patients With Sustained Acute Kidney Injury
Authors: Tanaka Tomohiro , Lentine Krista L. , Shi Qianyi , Vander Weg Mark , Axelrod David A.
Published: September 2023

Background.

Simultaneous liver-kidney transplant (SLK) allocation policy in the United States was revised in August 2017, reducing access for liver transplant candidates with sustained acute kidney injury (sAKI) and potentially adversely impacting vulnerable populations whose true renal function is overestimated by commonly used estimation equations.

Methods.

We examined national transplant registry data containing information for all liver transplant recipients from June 2013 to December 2021 to assess the impact of this policy change using instrumental variable estimation based on date of listing.

Results.

Posttransplant survival was compared for propensity-matched patients with sAKI who were only eligible for liver transplant alone (LTA_post; n = 638) after the policy change but would have been SLK-eligible before August 2017, with similar patients who were previously able to receive an SLK (SLK; n = 319). Overall posttransplant patient survival was similar at 3 y (81% versus 80%; P = 0.9). However, receiving an SLK versus LTA increased survival among African Americans (87% versus 61% at 3 y; P = 0.029). A trend toward survival benefit from SLK versus LTA, especially later in the follow-up period, was observed in recipients ≥ age 60 (3-y survival: 84% versus 76%; P = 0.2) and women (86% versus 80%; P = 0.2).

Conclusions.

The 2017 United Network for Organ Sharing SLK Allocation Policy was associated with reduced survival of African Americans with end-stage liver disease and sAKI and, potentially, older patients and women. Our study suggested the use of race-neutral estimation of renal function would ameliorate racial disparities in the SLK arena; however, further studies are needed to reduce disparity in posttransplant outcomes among patients with liver and kidney failure.
Impact of Tele-Triage Pathways on Short-Stay Admission after Transfer to a Regional Burn Center for Acute Burn Injury
Authors: Clark Nina M , Agoubi Lauren L , Gibbs Sarah , Stewart Barclay T , De Grauw Xinyao , Vavilala Monica S , Rivara Frederick P , Arbabi Saman , Pham Tam N
Published: September 2023

Background:

Regionalized care for burn-injured patients requires accurate triage. In 2016, we implemented a tele-triage system for acute burn consultations. We evaluated resource utilization following implementation, hypothesizing that this system would reduce short stay admissions and prioritize inpatient care for those with higher burn severity.

Methods:

We conducted a retrospective study of all transferred patients with acute burn injuries from 1/1/2010-12/31/2015 and 1/1/2017-12/31/2019. We evaluated proportions of short stay admissions (discharges <24 hours without operative intervention, ICU admission, or concern for non-accidental trauma) among patients transferred before (2010-2015) and after (2017-2019) triage system implementation. Multivariable Poisson regression was used to evaluate factors associated with short stay admissions. Interrupted time series analysis was used to evaluate the effect of the triage system.

Results:

There were 4688 burn transfers (3244 pre- and 1444 post-implementation) in the study periods. Mean age was higher post-implementation (32 vs 29 years, p<0.001). Median hospital LOS and ICU LOS were both 1 day higher, more patients underwent operative intervention (19% vs. 16%), and median time to first operation was 1 day lower post-implementation. Short stay admissions decreased from 50% (n=1624) to 39% (n=561), and patients were 17% less likely to have a short stay admission after implementation (aRR 0.83, 95% CI 0.8-0.9). Pediatric patients <15 years old composed 43% of all short stay admissions and were much more likely than adult patients to have a short stay admission independent of transfer timing (aRR 2.36, 95% CI 1.84-3.03).

Conclusions:

Tele-triage burn transfer center protocols reduced short-stay admissions and prioritized inpatient care for patients with more severe injuries. Pediatric patients remain more likely to have short stay admission after transfer.
Valid publication of four additional phylum names
Authors: Göker Markus , Oren Aharon
Published: September 2023

The International Code of Nomenclature of Prokaryotes (ICNP) now includes the phylum category. For the purpose of the valid publication of their names under the ICNP, we consider here four phyla. Slightly modified descriptions of ‘

Abditibacteriota

’ Tahon et al. 2018 and ‘

Desulfobacterota

’ Waite et al. 2020 are provided to meet the requirements of the ICNP for phylum names.

Methanobacteriota

is proposed as a substitute for ‘

Euryarchaeota

’ Garrity and Holt 2021, while Nanobdellota is proposed to replace ‘

Nanoarchaeota

’ Huber et al. 2002, based on the genus Nanobdella Kato et al. 2022.
Natural variation in the zinc-finger-encoding exon ofPrdm9affects hybrid sterility phenotypes in mice
Authors: AbuAlia Khawla FN , Damm Elena , Ullrich Kristian K , Mukaj Amisa , Parvanov Emil , Forejt Jiri , Odenthal-Hesse Linda
Published: September 2023

PRDM9-mediated reproductive isolation was first described in the progeny ofMus musculus musculus(MUS) PWD/Ph andMus musculus domesticus(DOM) C57BL/6J inbred strains. These male F1-hybrids fail to complete chromosome synapsis and arrest meiosis at prophase I, due to incompatibilities between thePrdm9gene and hybrid sterility locusHstx2. We identified fourteen alleles ofPrdm9in Exon 12, encoding the DNA-binding domain of the PRDM9 protein in outcrossed wild mouse populations from Europe, Asia, and the Middle East, eight of which are novel. The samePrdm9allele was found in all mice bearing introgressedt-haplotypes, encompassingPrdm9and inversions preventing recombination with wildtype Chr 17. We asked whether seven novelPrdm9alleles in MUS populations and thet-haplotype allele in one MUS and three DOM populations inducePrdm9-mediated reproductive isolation. The results show that only combinations of thedom2allele of DOM origin and the MUSmsc1allele ensure complete infertility of intersubspecific hybrids outside the context of inbred mouse strains. The results further indicate that the erasure of PRDM9msc1binding motifs may be shared by MUS mice from populations with differentPrdm9alleles, implicating that erased PRDM9 binding motifs may be uncoupled from their corresponding PRDM9 zinc finger arrays at the population level. Our data corroborate the model ofPrdm9-mediatedhybrid sterility beyond inbred strains of mice and suggest that sterility alleles ofPrdm9may be rare.
Sde Proteins Coordinate Ubiquitin Utilization and Phosphoribosylation to Establish and Maintain theLegionellaReplication Vacuole
Authors: Kotewicz Kristin M. , Zhang Mengyun , Kim Seongok , Martin Meghan S. , Chowdhury Atish Roy , Tai Albert , Scheck Rebecca A. , Isberg Ralph R.
Published: September 2023

TheLegionella pneumophilaSde family of translocated proteins promotes host tubular endoplasmic reticulum (ER) rearrangements that are tightly linked to phosphoribosyl-ubiquitin (pR-Ub) modification of Reticulon 4 (Rtn4). Sde proteins have two additional activities of unclear relevance to the infection process: K63 linkage-specific deubiquitination and phosphoribosyl modification of polyubiquitin (pR-Ub). We show here that the deubiquitination activity (DUB) stimulates ER rearrangements while pR-Ub protects the replication vacuole from cytosolic surveillance by autophagy. Loss of DUB activity is tightly linked to lowered pR-Ub modification of Rtn4, consistent with the DUB activity fueling the production of pR-Ub-Rtn4. In parallel, phosphoribosyl modification of polyUb, in a region of the protein known as the isoleucine patch, prevents binding by the autophagy adapter p62. An inability of Sde mutants to modify polyUb results in immediate p62 association, a critical precursor to autophagic attack. The ability of Sde WT to block p62 association decays quickly after bacterial infection, as predicted by the presence of previously characterizedL. pneumophilaeffectors that inactivate Sde and remove polyUb. In sum, these results show that the accessory Sde activities act to stimulate ER rearrangements and protect from host innate immune sensing in a temporal fashion.
A culture-based approach to study ecological interactions among the microbial species of the human scalp
Authors: Bhattacharya Swagatika , Roth Talia , Costa Suzannah , Santoro Ava , Mazza William , Coyte Katharine Z. , Clavaud Cécile , Foster Kevin R. , Kim Wook
Published: September 2023

The human scalp hosts an unusually low diversity microbiota dominated by three species:Cutibacterium acnes,Staphylococcus epidermidis, andMalassezia restricta, where characteristic shifts in species’ frequencies are associated with seborrheic dermatitis and dandruff. In order to better understand this important community, here we study the ecological interactions between these scalp species. We establish a new experimental model system that supports the growth of all three speciesin vitroand allows one to selectively enumerate each species from co-culture. Our work reveals the potential for strong ecological interactions within the scalp community. In particular,C. acnesgreatly benefits from the presence ofM. restricta, but harms it in return (exploitation), whileS. epidermidissuppresses bothM. restrictaandC. acnes. Our data suggest that the shifts in composition seen in compromised scalps are influenced by ecological interactions between species. We argue that the scalp microbiome should be viewed as an ecological system where species interactions have the potential to contribute to health outcomes.

Importance

Our bodies are home to diverse communities of microorganisms, our microbiome, which can be critical for health and wellbeing. The human scalp hosts a relatively simple community dominated by three species: two bacteria,Cutibacterium acnesandStaphylococcus epidermidis, and one fungus,Malassezia restricta. Both dandruff and seborrheic dermatitis are strongly associated with characteristic shifts in the frequencies of these three species. However, how these species affect one another and behave as a community remains poorly understood. Here, we develop a simple experimental system to empirically study how these three species interact and affect one another for the first time. We find thatS. epidermidisgreatly suppresses the growth of the other species, whileC. acnesspecifically exploitsM. restricta. Our work suggests that the human scalp is an ecological system in which species interactions have the potential to affect health outcomes.
Towards interpretable learned representations for Ecoacoustics using variational auto-encoding
Authors: Gibb K. A. , Eldridge A. , Sandom C. J. , Simpson I. J. A.
Published: September 2023

Abstract

Ecoacoustics is an emerging science that seeks to understand the role of sound in ecological processes. Passive acoustic monitoring is increasingly being used to collect vast quantities of whole-soundscape audio recordings in order to study variations in acoustic community activity across spatial and temporal scales. However, extracting relevant information from audio recordings for ecological inference is non-trivial. Recent approaches to machine-learned acoustic features appear promising but are limited by inductive biases, crude temporal integration methods and few means to interpret downstream inference. To address these limitations we developed and trained a self-supervised representation learning algorithm -a convolutional Variational Auto-Encoder (VAE) -to embed latent features from acoustic survey data collected from sites representing a gradient of habitat degradation in temperate and tropical ecozones and use prediction of survey site as a test case for interpreting inference. We investigate approaches to interpretability by mapping discriminative descriptors back to the spectro-temporal domain to observe how soundscape components change as we interpolate across a linear classification boundary traversing latent feature space; we advance temporal integration methods by encoding a probabilistic soundscape descriptor capable of capturing multi-modal distributions of latent features over time. Our results suggest that varying combinations of soundscape components (biophony, geophony and anthrophony) are used to infer sites along a degradation gradient and increased sensitivity to periodic signals improves on previous research using time-averaged representations for site classification. We also find the VAE is highly sensitive to differences in recorder hardware’s frequency response and demonstrate a simple linear transformation to mitigate the effect of hardware variance on the learned representation. Our work paves the way for development of a new class of deep neural networks that afford more interpretable machine-learned ecoacoustic representations to advance the fundamental and applied science and support global conservation efforts.
Axial de-scanning using remote focusing in the detection arm of light-sheet microscopy
Authors: Dibaji Hassan , Nasaban Shotorban Ali Kazemi , Grattan Rachel M , Lucero Shayna , Schodt David J. , Lidke Keith A. , Petruccelli Jonathan , Lidke Diane S. , Liu Sheng , Chakraborty Tonmoy
Published: September 2023

The ability to image at high speeds is necessary for biological imaging to capture fast-moving or transient events or to efficiently image large samples. However, due to the lack of rigidity of biological specimens, carrying out fast, high-resolution volumetric imaging without moving and agitating the sample has been a challenging problem. Pupil-matched remote focusing has been promising for high NA imaging systems with their low aberrations and wavelength independence, making it suitable for multicolor imaging. However, owing to the incoherent and unpolarized nature of the fluorescence signal, manipulating this emission light through remote focusing is challenging. Therefore, remote focusing has been primarily limited to the illumination arm, using polarized laser light to facilitate coupling in and out of the remote focusing optics. Here, we introduce a novel optical design that can de-scan the axial focus movement in the detection arm of a microscope. Our method splits the fluorescence signal into S and P-polarized light, lets them pass through the remote focusing module separately, and combines them with the camera. This allows us to use only one focusing element to perform aberration-free, multi-color, volumetric imaging without (a) compromising the fluorescent signal and (b) needing to perform sample/detection-objective translation. We demonstrate the capabilities of this scheme by acquiring fast dual-color 4D (3D space + time) image stacks with an axial range of 70 μm and camera-limited acquisition speed. Owing to its general nature, we believe this technique will find its application in many other microscopy techniques that currently use an adjustable Z-stage to carry out volumetric imaging, such as confocal, 2-photon, and light sheet variants.
Stacking of PRRs in potato to achieve enhanced resistance againstPhytophthora infestans
Authors: Torres Ascurra Yerisf C. , Wouters Doret , Visser Richard G. F. , Nürnberger Thorsten , Vleeshouwers Vivianne G. A. A.
Published: September 2023

Plants employ pattern recognition receptors (PRRs) to sense pathogen-associated molecular patterns (PAMPs) or apoplastic effectors at the plant cell surface, as well as nucleotide-binding domain leucine-rich-repeat-containing receptors (NLRs) to sense effectors inside the plant cell. Breeding for potato resistance toP. infestanshas focused on the use of NLRs, however, these genes are typically quickly overcome since the matching avirulence genes evolve exceptionally quickly. Here, we stacked two PRRs,PERUandRLP23, that recognize the rather conservedPhytophthoraPAMPs Pep-13/25 and nlp20, respectively, in the potato cultivar Atlantic, and evaluated their effect onP. infestansresistance. We found that PERU and RLP23 cooperate for the early immune responses like the accumulation of reactive oxygen species (ROS) and production of ethylene by recognizing their corresponding PAMPs. Furthermore, we show that potato plants overexpressing these two PRRs are slightly less affected byP. infestanscompared to the single transformants. Together, our data suggest that pyramiding of surface receptors can provide additional enhanced resistance against pathogens, however, more effective or synergistic combinations that may include intracellular NLR receptors should be explored.
Modulation of Arterial Intima Stiffness by Disturbed Blood Flow
Authors: Bywaters Briana C. , Trache Andreea , Rivera Gonzalo M.
Published: September 2023

Background

The intima, comprising the endothelium and the subendothelial matrix, plays a crucial role in the development of atherosclerotic plaques, especially in bifurcations and curved segments of arteries. The mechanical stress arising from disturbed blood flow (d-flow) and the stiffening of the arterial wall contributes to endothelial dysfunction. However, the specific impacts of these physical forces on the mechanical environment of the intima remain undetermined. To address this gap in knowledge, we investigated whether inhibiting collagen crosslinking could ameliorate the detrimental effects of persistent d-flow on the mechanical properties of the intima.

Methods

To explore this hypothesis, we performed partial ligation (PCL) of the left carotid artery (LCA) in male and female C57BL/6J mice, inducing d-flow. The right carotid artery (RCA) served as an internal control. Carotids were collected two days and two weeks after PCL to study acute and chronic effects of d-flow on the mechanical phenotype of the intima. To decouple the chronic effects of d-flow from the ensuing arterial wall stiffening, we used subcutaneous implants delivering either phosphate-buffered saline (Saline) or 150 mg/kg/day of β-aminopropionitrile (BAPN), an inhibitor of elastin and collagen crosslinking lysyl oxidase (LOX) and LOX-like (LOXL) enzymes. Atomic force microscopy (AFM) measurements allowed us to determine stiffness of the endothelium and the denuded subendothelial matrix inen facecarotid preparations. In addition, we determined the stiffness of human aortic endothelial cells (HAEC) cultured on soft and stiff hydrogels.

Results

Acute exposure to d-flow caused a slight decrease in endothelial stiffness in male mice but had no effect on the stiffness of the subendothelial matrix in either sex. Regardless of sex, the intact endothelium was softer than the subendothelial matrix. In contrast, exposure to chronic d-flow led to a substantial increase in the endothelial and subendothelial stiffness in both sexes. The effects of chronic d-flow were largely prevented by concurrent BAPN administration. Notably, the subendothelial matrix of ligated, BAPN-treated arteries was softer than that of unligated, saline-treated counterparts. Furthermore, HAEC displayed reduced stiffness when cultured on soft vs. stiff hydrogels.

Conclusions

Exposure to chronic d-flow results in marked stiffening of arterial intima, which can be effectively prevented by pharmacological inhibition of LOX/LOXL enzymes.

Highlights

Acute exposure to d-flow slightly softens the endothelium in males.

Chronic exposure to d-flow causes stiffening of the arterial intima.

Inhibition of LOX/LOXL enzymes prevents intimal stiffening arising from chronic d-flow.
In utero human cytomegalovirus infection expands NK cell-like FcγRIII-expressing CD8+ T cells that mediate antibody-dependent functions
Authors: Semmes Eleanor C , Nettere Danielle R , Nelson Ashley N , Hurst Jillian H , Cain Derek , Burt Trevor D , Kurtzberg Joanne , Reeves R. Keith , Coyne Carolyn B , Fouda Genevieve G , Pollara Justin , Permar Sallie R , Walsh Kyle M
Published: September 2023

Human cytomegalovirus (HCMV) profoundly modulates host T and natural killer (NK) cells across the lifespan, expanding unique effector cells bridging innate and adaptive immunity. Though HCMV is the most common congenital infection worldwide, how this ubiquitous herpesvirus impacts developing fetal T and NK cells remains unclear. Using computational flow cytometry and transcriptome profiling of cord blood from neonates with and without congenital HCMV (cCMV) infection, we identify major shifts in fetal cellular immunity marked by an expansion of Fcγ receptor III (FcγRIII)-expressing CD8+ T cells (FcRT) following HCMV exposure in utero. FcRT cells from cCMV-infected neonates express a cytotoxic NK cell-like transcriptome and mediate antigen-specific antibody-dependent functions including degranulation and IFNγ production, the hallmarks of NK cell antibody-dependent cellular cytotoxicity (ADCC). FcRT cells may represent a previously unappreciated effector population with innate-like functions that could be harnessed for maternal-infant vaccination strategies and antibody-based therapeutics in early life.
LUZP1 regulates the assembly of stress fibers by promoting maturation of contractile actomyosin bundles
Authors: Wang Liang , Tsang Hoi Ying , Yan Ziyi , Tojkander Sari , Ciuba Katarzyna , Kogan Konstantin , Liu Xiaonan , Zhao Hongxia
Published: September 2023

Contractile actomyosin bundles play crucial roles in various physiological processes, including cell migration, morphogenesis, and muscle contraction. The intricate assembly of actomyosin bundles involves the precise alignment and fusion of myosin II filaments, yet the underlying mechanisms and factors involved in these processes remain elusive. Our study reveals that LUZP1, a leucine zipper protein, plays a central role in orchestrating the formation of thick actomyosin bundles. Loss of LUZP1 caused abnormal cell morphogenesis, migration, and the ability to exert forces on the environment. Importantly, knockout of LUZP1 results in significant defects in the concatenation and persistent association of myosin II filaments, severely impairing the assembly of myosin II stacks. The disruption of these processes in LUZP1 knockout cells provides mechanistic insights into the defective assembly of thick ventral stress fibers and the associated cellular contractility abnormalities. Overall, these results significantly contribute to our understanding of the molecular mechanism involved in actomyosin bundle formation and highlight the essential role of LUZP1 in this process.
The chloroplastic phosphate transporter CrPHT4-7 supports phosphate homeostasis and photosynthesis in Chlamydomonas
Authors: Tóth Dávid , Kuntam Soujanya , Ferenczi Áron , Vidal-Meireles André , Kovács László , Wang Lianyong , Sarkadi Zsuzsa , Migh Ede , Szentmihályi Klára , Tengölics Roland , Neupert Juliane , Bock Ralph , Jonikas Martin C. , Molnar Attila , Tóth Szilvia Z.
Published: September 2023

In eukaryotic cells, phosphorus is assimilated and utilized primarily as phosphate (Pi). Pi homeostasis is mediated by transporters that have not yet been adequately characterized in green algae. This study reports on CrPHT4-7 fromChlamydomonas reinhardtii, a member of the PHT4 transporter family, which exhibits remarkable similarity to AtPHT4;4 fromArabidopsis thaliana, a chloroplastic ascorbate transporter. Using fluorescent protein tagging we show that CrPHT4-7 resides in the chloroplast envelope membrane.Crpht4-7mutants, generated by the CRISPR/Cas12a-mediated single-strand templated repair, show retarded growth especially in high light, enhanced sensitivity to phosphorus limitation, reduced ATP level, strong ascorbate accumulation and diminished non-photochemical quenching in high light. Conversely, CrPHT4-7 overexpressing lines exhibit enhanced biomass accumulation under high light conditions in comparison with the wild-type strain. Expressing CrPHT4-7 in a yeast strain lacking Pi transporters substantially recovered its slow growth phenotype demonstrating that it transports Pi. Even though CrPHT4-7 shows a high degree of similarity to AtPHT4;4, it does not display any significant ascorbate transport activity in yeast or intact algal cells. Thus, the results demonstrate that CrPHT4-7 functions as a chloroplastic Pi transporter essential for maintaining Pi homeostasis and photosynthesis inChlamydomonas reinhardtii.

One-sentence summary

We demonstrate that the CrPHT4-7 transporter ofChlamydomonas reinhardtiiis located in the chloroplast envelope membrane and contributes to maintaining phosphate homeostasis and photosynthesis.