bluuebunny/crossref_metadata_2025_split huggingface dataset:
Secreted Effector Proteins of Poplar Leaf Spot and Stem Canker Pathogen Sphaerulina musiva Manipulate Plant Immunity and Contribute to Virulence in Diverse Ways
Authors: Zhao Yao , Zheng Xinyue , Tabima Javier F. , Zhu Sheng , Søndreli Kelsey L. , Hundley Hope , Bauer Diane , Barry Kerrie , Zhang Yaxin , Schmutz Jeremy , Wang Yuanchao , LeBoldus Jared M. , Xiong Qin 
Published: August 2023

Fungal effectors play critical roles in manipulating plant immune responses and promoting colonization. Sphaerulina musiva is a heterothallic ascomycete fungus that causes Septoria leaf spot and stem canker disease in poplar ( Populus spp.) plantations. This disease can result in premature defoliation, branch and stem breakage, increased mortality, and plantation failure. However, little is known about the interaction between S. musiva and poplar. Previous work predicted 142 candidate secreted effector proteins in S. musiva (SmCSEPs), 19 of which were selected for further functional characterization in this study. SmCSEP3 induced plant cell death in Nicotiana benthamiana, while 8 out of 19 tested SmCSEPs suppressed cell death. The signal peptides of these eight SmCSEPs exhibited secretory activity in a yeast signal sequence trap assay. Confocal microscopy revealed that four of these eight SmCSEPs target both the cytoplasm and the nucleus, whereas four predominantly localize to discrete punctate structures. Pathogen challenge assays in N. benthamiana demonstrated that the transient expression of six SmCSEPs promoted Fusarium proliferatum infection. The expression of these six SmCSEP genes were induced during infection. SmCSEP2, SmCSEP13, and SmCSEP25 suppressed chitin-triggered reactive oxygen species burst and callose deposition in N. benthamiana. The candidate secreted effector proteins of S. musiva target multiple compartments in the plant cell and modulate different pattern-triggered immunity pathways. [Formula: see text] The author(s) have dedicated the work to the public domain under the Creative Commons CC0 “No Rights Reserved” license by waiving all of his or her rights to the work worldwide under copyright law, including all related and neighboring rights, to the extent allowed by law, 2023.
Hydroxyurea attenuates hepatic stellate cell proliferation in vitro and liver fibrogenesis in vivo
Authors: Haijer Floris , Koets‐Shajari Shiva , Heegsma Janette , Serna‐Salas Sandra , Blokzijl Tjasso , Buist‐Homan Manon , Moshage Han , Faber Klaas Nico 
Published: August 2023

AbstractLiver fibrosis results from excessive proliferation of, and collagen production by hepatic stellate cells (HSCs) that is caused by chronic liver injury. No drugs are available to cure liver fibrosis. Hydroxyurea is an anti‐proliferative drug that is used in benign and malignant disorders. Here, we studied the effect of hydroxyurea on primary HSCs and its anti‐fibrotic effect in the CCl4 mouse model of liver fibrosis. Primary rat HSCs were cultured in the absence or presence of hydroxyurea (0.1–1.0 mmol/L). CCl4 or vehicle was administered to C57BL/6/J mice for 4 weeks, with or without hydroxyurea (100 mg/kg/day) co‐treatment. We used real‐time cell proliferation analysis, Oil Red O (lipid droplet) staining, immunohistochemistry, Acridine Orange staining (apoptosis), Sytox green staining (necrosis), RT‐qPCR, ELISA, and Western Blotting for analysis. Hydroxyurea dose‐dependently suppressed lipid droplet‐loss and mRNA levels of Col1α1 and Acta2 in transdifferentiating HSCs. In fully‐activated HSCs, hydroxyurea dose‐dependently attenuated PCNA protein levels and BrdU incorporation, but did not reverse Col1α1 and Acta2 mRNA expression. Hydroxyurea did not induce apoptosis or necrosis in HSCs or hepatocytes. Hydroxyurea suppressed accumulation of desmin‐positive HSCs and hepatic collagen deposition after CCl4 treatment. CCl4‐induced regenerative hepatocyte proliferation, Col1α1 and Acta2 mRNA expression and α‐SMA protein levels were not affected. This study demonstrates that hydroxyurea inhibits HSC proliferation in vitro and attenuates early development of liver fibrosis in vivo, while preserving hepatocyte regeneration after toxic insults by CCl4. Thus, hydroxyurea may have therapeutic value against liver fibrosis.
Continuous peripheral nerve blocks for analgesia following painful ambulatory surgery: a review with focus on recent developments in infusion technology
Authors: Finneran John J. , Ilfeld Brian M. 
Published: August 2023

Purpose of reviewContinuous peripheral nerve blocks (cPNB) decrease pain scores and opioid consumption while improving patient satisfaction following ambulatory surgery. This review focuses on the history and evolution of ambulatory cPNBs, recent developments in infusion technology that may prolong the duration of analgesia, optimal choice of cPNB for various surgical procedures, and novel analgesic modalities that may prove to be alternatives or supplements to cPNBs.Recent findingsThe primary factor limiting the duration of an ambulatory cPNB is the size of the local anesthetic reservoir. Recent evidence suggests the use of automated boluses, as opposed to continuous infusions, may decrease the rate of consumption of local anesthetic and, thereby, prolong the duration of analgesia. Utilizing a long-acting local anesthetic (e.g. ropivacaine) for initial block placement and an infusion start-delay timer may further increase this duration.SummaryPatients undergoing painful ambulatory surgery are likely to have less pain and require fewer opioid analgesics when receiving a cPNB for postoperative analgesia. Advances in electronic pumps used for cPNBs may increase the duration of these benefits.
Etiology, management, and sequela of postdural puncture headache
Authors: Taraskiewicz Daniel , Sheeran Jessica , De Marco Paul , Tiouririne Mohamed , Elkassabany Nabil 
Published: August 2023

Purpose
The purpose of this article is to provide readers with a concise overview of the cause, incidence, treatment of, and sequalae of postdural puncture headaches (PDPH). Over the past 2 years, much data has been published on modifiable risk factors for PDPH, treatments for PDPH, and sequalae of PDPH particularly long-term.

Recent findings
There is emerging data about how modifiable risk factors for PDPH are not as absolute as once believed. There have been several new meta-analysis and clinical trials published, providing more data about effective therapies for PDPH. Significantly, much recent data has come out about the sequalae, particularly long-term of dural puncture.

Summary
Emerging evidence demonstrates that in patients who are at low risk of PDPH, needle type and gauge may be of no consequence in a patient developing a PDPH. Although epidural blood patch (EBP) remains the gold-standard of therapy, several other interventions, both medical and procedural, show promise and may obviate the need for EBP in patients with mild–moderate PDPH. Patients who endure dural puncture, especially accidental dural puncture (ADP) are at low but significant risk of developing short term issues as well as chronic pain symptoms.
Preclinical models to understand the biology and to discover new targets in brain metastases
Authors: Kindt Nadège , Kotecki Nuria , Awada Ahmad 
Published: August 2023

Purpose of review
Incidence of brain metastases increases overtime therefore it is important to rapidly progress in the discovery of new strategies of treatment for these patients. In consequence, more and more preclinical models of brain metastases (BM) are established to study new treatments for melanoma, lung, and breast cancer BM. Here, we reviewed the most recent findings of new drugs assessed in BM mouse preclinical models.

Recent findings
BM are a common metastatic site of several types of solid cancers and can be difficult to treat due to the unique environment of the brain and the blood-brain barrier. Currently, several preclinical models of BM have been demonstrated that new molecular targeted therapies, small metabolic inhibitors, immunotherapies or a combination of these drugs with radiotherapy lead to a reduction of BM growth and an improvement of mouse survival.

Summary
The use of preclinical models of BM is crucial to discover new treatment strategies for patients with BM. In the last years, some new drugs have been highlighted in preclinical models and are now tested in clinical trials including patients with brain metastases.
Controversies in central nervous system prophylaxis of high-risk diffuse large B-cell lymphoma
Authors: Bobillo Sabela , Wilson Matthew R. , Cwynarski Kate 
Published: August 2023

Purpose of review
Central nervous system (CNS) relapse in patients with diffuse large B-cell lymphoma (DLBCL) is an uncommon but devastating complication with an overall survival of less than 6 months. This article will review the recent updates on CNS prophylaxis including new potential advances in the identification of high-risk patients.

Recent findings
The identification of patients at a high risk of CNS relapse is based on clinical and biological features has improved over recent years; however, the of different CNS prophylaxis strategies including intrathecal chemotherapy and high-dose methotrexate have been recently questioned in several large retrospective studies. The analysis of cell-free circulating tumor DNA (ctDNA) in the cerebrospinal fluid has been shown to identify patients with a high risk of CNS involvement and work is ongoing to identify how this can be used as a prognostic biomarker.

Summary
Recent clinical retrospective data have questioned the effectiveness of intrathecal and high-dose methotrexate in the prevention of CNS relapse in high-risk DLBCL patients. The role of more sensitive methods to detect CNS involvement and the benefit of novel therapies in CNS relapse prevention are currently under evaluation.
Tailor-made three-dimensional printing vaginal pessary to treat pelvic organ prolapse: a pilot study
Authors: Lin Yi-Hao , Lim Chor-Kheng , Chang Shuenn-Dyh , Chiang Chih-Chien , Huang Chun-Hung , Tseng Ling-Hong 
Published: August 2023

Abstract

Objective
This study aimed to apply three-dimensional (3D) printing technology to treat women with pelvic organ prolapse (POP) and to evaluate efficacy based on the improvement by quality of life (QOL) questionnaires.

Methods
This was a pilot study at a tertiary urogynecology unit in Taiwan. Between January 2021 and June 6, 2021, participants who opted for self-management using Gellhorn pessaries to treat symptomatic POP were enrolled. For each woman, the original Gellhorn pessary was placed into the vagina to restore the prolapsed tissues and under transvaginal ultrasound guided to evaluate the gap which the Gellhorn pessary cannot cover. Otoform (an impression silicone) was used to make a model and have it hooked onto Gellhorn pessary (template). We collected templates and then applied 3D printing to customize the silicone vaginal pessary. All women completed multiple validated QOL questionnaires at baseline and at 3 and 6 months.

Results
Six women completed the study. The QOL questionnaires revealed significant improvements across the board.

Conclusions
Our study demonstrates that a tailor made 3D pessary can be used for women with POP. A customized pessary can be made with the help of transvaginal ultrasound and 3D printing technology.
POSTINFECTIOUS NONPARANEOPLASTIC AUTOIMMUNE RETINOPATHY IN THE PEDIATRIC AGE GROUP: A HIGH INDEX OF SUSPICION, MULTIMODAL IMAGING AND EARLY TREATMENT CAN RESTORE VISION
Authors: R Neena , Borgohain Ashapurna , Anantharaman Giridhar , Baby Neena 
Published: August 2023

Purpose:
To report a case of nonparaneoplastic autoimmune retinopathy in a pediatric patient who showed excellent visual recovery with early diagnosis and prompt treatment.

Methods:
Retrospective case report.

Results:
A 5-year-old girl presented to us with bilateral profound vision loss of subacute onset after an episode of high fever, without any previous visual abnormality. A diagnosis of nonparaneoplastic autoimmune retinopathy was made based on history, clinical findings, and multimodal imaging. IV methylprednisolone was started urgently followed by oral steroid. The visual acuity showed good improvement along with gradual restoration of anatomy of retinal layers in optical coherence tomography over a period of 3 months.

Conclusion:
Our case highlights the importance of suspecting nonparaneoplastic autoimmune retinopathy in pediatric patients presenting with sudden bilateral painless progressive loss of vision without prior visual difficulties and the role of multimodal imaging to aid in diagnosis. The recovery of vision with restoration of the photoreceptor layer also shows the nature of the disease to recover with early intervention despite a negative antiretinal antibody test but with features highly suggestive of nonparaneoplastic autoimmune retinopathy.
Hydroxyapatite Use in Repair of Lateral Skull Base CSF Leaks Via Transmastoid Approach: When Does It Work?
Authors: Shah Rema , Kveton John , Schwartz Nofrat 
Published: August 2023

Objective
The objective of this study is to evaluate the efficacy and outcomes of using a transmastoid approach with hydroxyapatite cement to repair lateral skull base cerebrospinal fluid (CSF) leaks.

Study Design
Retrospective cohort study.

Setting
Tertiary-level care hospital.

Patients
Surgical patients 18 years or older between 2013 and 2022 with spontaneous CSF leak.

Interventions
Trans-mastoid approach for skull base repair using hydroxyapatite cement.

Main Outcome Measures
Failure rate of repair; location and size of defect, patient demographic factors.

Results
Of the 60 total defects (55 patients, 5 bilateral repairs) that underwent CSF leak repair using hydroxyapatite cement, the success rate was 91.66% (55 successful repairs). The average defect size in unsuccessful repairs was 1.15 cm compared with 0.71 cm for successful repairs. In addition, 80% (4/5) of the failed repairs were in the tegmen tympani region. Higher failure rate was noted in women (3/5) and in former smokers (4/5). Average time to recurrent symptoms was 1.75 years in the failed repair cohort. Of the patients with failed repairs, 4/5 were prescribed acetazolamide before their second procedure with successful second repair. In addition, five patients experienced postoperative headaches, three (5.4%) of whom required placement of VP shunts to relieve increased intracranial pressure. Two patients (3.6%) had complications of either infection or hearing loss.

Conclusions
Transmastoid approach utilizing hydroxyapatite is a successful approach for CSF leak repair, with a low complication and failure rate. Women, prior smoking history, and larger defects in the tegmen tympani region may need alternative materials or approach for repair. Long follow-up is warranted as recurrence of symptoms might be delayed. In cases of benign intracranial hypertension, adjuvant treatment with either acetazolamide or VP shunt placement may prevent failures.
The common trisomy syndromes, their cardiac implications, and ethical considerations in care
Authors: Kosiv Katherine A. , Mercurio Mark R. , Carey John C. 
Published: August 2023

Purpose of review
To review the incidence of congenital heart disease in the trisomies, highlight the history of cardiac surgery in trisomy 21 comparing it to the increase in cardiac surgery in trisomies 13 and 18, discuss ethical issues specific to trisomies 13 and 18, and suggest a pathway of shared decision-making in the management of congenital heart disease in trisomy 13 and 18, specifically congenital heart surgery.

Recent findings
Congenital heart disease is prevalent in the trisomies and the management of these defects, especially surgical intervention, has changed. In the late 20th century, survival after cardiac surgery in trisomy 21 vastly improved, significantly decreasing morbidity and mortality secondary to pulmonary hypertension. Similarly, procedures and surgeries have been performed with increasing frequency in trisomy 13 and 18 patients and concomitantly, survival in this patient population is increasing. Yet across the United States, the willingness to perform cardiac surgery in trisomy 13 and 18 is variable, and there is ethical controversy about the correct action to take. To address this concern, a shared decision-making approach with an informed parent(s) is advised.

Summary
As the care and management of congenital heart disease changed in trisomy 21, so too it has with trisomy 13 and 18. Physicians and parents should develop goal-directed treatment plans balancing the risk versus benefit and consider cardiac surgical repair if feasible and beneficial.
EarWell Infant Ear Molding Device: Experience and Parent Survey
Authors: Ahmed Moumen , Al Saadawi Ghaith , Mendonca Derek A. 
Published: August 2023

Background:
EarWell infant ear molding device is a noninvasive, nonsurgical option to treat ear deformities in early infancy. There are no studies involving the parents’ perspective to the use of the EarWell.

Aim:
To investigate our experience with EarWell infant ear molding device and to assess the parents’ satisfaction.

Study Design:
A retrospective case series study of infants with congenital ear deformities who were treated with EarWell device from October 2021 to November 2022. Demographic and clinical data were collected. Clinical photographs were obtained before, during, and after treatment. Parents’ satisfaction level was assessed through telephone encounters and surveys, and issues associated with device application were identified. Clinical improvement of ear deformity was graded into poor, fair, good, and excellent.

Results:
A total of 9 patients with congenital ear deformities were identified and included in this study (7 bilateral deformities and 2 unilateral deformities). The mean adjusted age of the initial treatment is 17 weeks (4–23 weeks), and the mean treatment duration is 5.7 weeks. The authors received full 8 responses from the parents’ survey, and all parents were satisfied with post-treatment results (4 satisfied, 1 fully satisfied, and 2 very satisfied). Issues associated with device application were 3 superficial skin ulcers and 4 skin irritation. Clinical Improvement grades were: 5 excellent improvement, 2 good improvement, and 2 fair improvement.

Conclusions:
On the basis of our experience, the EarWell device has shown a high success rate and a low complication rate. It is well accepted by parents, but it needs close follow-up to detect minor device-related issues. The device is safe for multiple skin types.
Changes in local immune status in tonsillopharyngitis under pathogenic therapy with the BNO 1030 extract: a randomized, comparative, parallel-group, single-center study
Authors: Savlevich Elena L. , Kozlov Vladimir S. , Gaponov Andrey M. , Gerasimov Andrey N. , Markus Petr V. , Yakushenko Elena V. , Doroshchenko Natalia E. , Kozlov Ivan G. 
Published: August 2023

AbstractAim of studyThe present study aimed to evaluate anti-inflammatory and immunomodulating properties of BNO 1030 (Tonsilgon® N) and its direct effect on the indicators of the local immunity of oropharyngeal mucosa in patients with acute tonsillopharyngitis (TP) or exacerbation of chronic TP without evident systemic inflammatory syndrome.Materials and methodsA total of 60 adult patients with acute TP or exacerbation of chronic TP without severe systemic inflammatory syndrome were randomly divided into 2 groups: Group 1 L 30 patients took BNO 1030 (Tonsilgon® N), Group 2 L 30 patients took sage tablets according to the summary of product characteristics during 7 days. During 3 visits (day 1, day 3, day 7) symptoms and oropharyngeal mucosa condition were evaluated using a 10-point visual analogue scale (VAS). Local immunity parameters of oropharyngeal mucosa (cytokines: IL-1β, IL-6, IL-8, IL-10, IL-17, TNF-α, and lysozyme, lactoferrin, sIgA) were determined by ELISA and by real time polymerase chain reaction.ResultsReduction of the main symptoms was significantly faster under BNO 1030 therapy than under sage therapy. In BNO 1030 group reduction of clinical symptoms correlated with the onset of action and the local immunological parameters. During BNO 1030 treatment IL-1β, IL-6, and IL-8 mRNA levels decreased below the levels in healthy controls, while, the immune factors lysozyme, lactoferrin and sIgA increased. Therapy with sage tablets did not affect local immunity parameters.ConclusionBoth treatment regimens resulted in elimination of clinical signs and mucosal pharyngeal barrier regeneration. In contrast to the sage tablets, BNO 1030 can also affect local mucosal immunity via regulating the balance of pro- and anti-inflammatory factors.Study highlightsThis study can answer the question regarding influence on main local immunity parameters of subjects with tonsillitisThe one of main task of this study is to evaluate what local immune parameters of oral cavity are most changeableTonsilgon N usage is not decrease main local immunity parameters such as IL-1β, IL-8, lysozyme and lactoferrinThis study evaluated the functional condition of mucosal immunity of oral cavity in subjects with tonsillopharingitis
The heme exporter FLVCR regulates mitochondrial biogenesis and redox balance in the hematophagous insectRhodnius prolixus
Authors: Walter-Nuno Ana Beatriz , Taracena-Agarwal Mabel , Oliveira Matheus P. , Oliveira Marcus F. , Oliveira Pedro L. , Paiva-Silva Gabriela O. 
Published: August 2023

AbstractHeme is a prosthetic group of proteins involved in vital physiological processes in aerobic organisms. It participates in redox reactions crucial for cell metabolism due to the variable oxidation state of its central iron atom. However, excessive heme can be cytotoxic due to its prooxidant properties. Therefore, the control of intracellular heme levels ensures the survival of organisms, especially those that deal with high concentrations of heme during their lives, such as hematophagous insects. The feline leukemia virus C receptor (FLVCR) is a membrane protein responsible for heme transport in mammalian cells. In our study, we found that RpFLVCR serves as a heme exporter in the midgut of the hematophagous insectRhodnius prolixus, a vector for Chagas disease. Silencing RpFLVCR decreased hemolymphatic heme levels and increased the levels of intracellular dicysteinyl-biliverdin, a product ofR. prolixusheme degradation, indicating heme retention inside midgut cells. FLVCR silencing led to increased expression of heme oxygenase (HO), ferritin, and mitoferrin mRNAs while downregulating the iron importers Malvolio 1 and 2. In contrast, HO gene silencing increased FLVCR and Malvolio expression and downregulated ferritin, revealing crosstalk between heme degradation/export and iron transport/storage pathways. Furthermore, RpFLVCR silencing strongly increased oxidant production and lipid peroxidation, reduced cytochrome c oxidase activity and activated mitochondrial biogenesis, effects not observed in RpHO-silenced insects. These data support FLVCR function as a heme exporter, playing a pivotal role in heme/iron metabolism and maintenance of redox balance, especially in an organism adapted to face extremely high concentrations of heme.