bluuebunny/crossref_metadata_2025 huggingface dataset:
Genetic and Phenotypic Characterization of Xanthomonas Species Pathogenic in Wheat in Uruguay
Authors: Clavijo Felipe , Curland Rebecca D. , Croce Valentina , Lapaz María I. , Dill-Macky Ruth , Pereyra Silvia , Siri María I.
Published: August 2021

Bacterial diseases affecting wheat production in Uruguay are an issue of growing concern yet remain largely uninvestigated in the region. Surveys of 61 wheat fields carried out from 2017 to 2019 yielded a regional collection of 63 strains identified by 16S rRNA gene analysis as Xanthomonas spp. A real-time PCR protocol with species-specific primers previously reported allowed the identification of 44 strains as X. translucens, the causal agent of bacterial leaf streak (BLS) in wheat and other cereal crops. Multilocus sequence analysis of four housekeeping genes (dnaK, fyuA, gyrB, and rpoD) revealed that these strains were most closely related to X. translucens pv. undulosa, the pathovar that is most commonly associated with BLS of wheat. Multilocus sequence typing was applied to examine the genetic diversity of X. translucens strains. Strains were assigned to four different sequence types, three of which were previously reported globally. Additionally, 17 Xanthomonas strains not belonging to X. translucens were obtained from diseased wheat leaves. Phylogenetic analysis showed that these strains are closely related to X. prunicola and clustered together with previously uncharacterized Xanthomonas strains isolated from wheat in Minnesota. In planta pathogenicity assays carried out on a BLS-susceptible wheat cultivar showed that X. translucens pv. undulosa strains caused brown necrosis symptoms typical of BLS, whereas non-translucens Xanthomonas sp. strains elicited an atypical symptom of dry necrosis. These findings suggest that local wheat fields are affected by X. translucens pv. undulosa and by a new wheat pathogen within the Xanthomonas genus.
Xanthomonas oryzae pv. oryzae Exoribonuclease R Is Required for Complete Virulence in Rice, Optimal Motility, and Growth Under Stress
Authors: Roy Sharmila , Mittal Pragya , Tayi Lavanya , Bondada Sahitya , Ray Malay K. , Patel Hitendra K. , Sonti Ramesh V.
Published: August 2021

Exoribonuclease R (RNase R) is a 3′ hydrolytic exoribonuclease that can degrade structured RNA. Mutation in RNase R affects virulence of certain human pathogenic bacteria. The aim of this study was to determine whether RNase R is necessary for virulence of the phytopathogen that causes bacterial blight in rice, Xanthomonas oryzae pv. oryzae (Xoo). In silico analysis has indicated that RNase R is highly conserved among various xanthomonads. Amino acid sequence alignment of Xoo RNase R with RNase R from various taxa indicated that Xoo RNase R clustered with RNase R of order Xanthomonadales. To study its role in virulence, we generated a gene disruption mutant of Xoo RNase R. The Xoo rnr– mutant is moderately virulence deficient, and the complementing strain (rnr–/pHM1::rnr) rescued the virulence deficiency of the mutant. We investigated swimming and swarming motilities in both nutrient-deficient minimal media and nutrient-optimal media. We observed that RNase R mutation has adversely affected the swimming and swarming motilities of Xoo in optimal media. However, in nutrient-deficient media only swimming motility was noticeably affected. Growth curves in optimal media at suboptimal temperature (15°C cold stress) indicate that the Xoo rnr– mutant grows more slowly than the Xoo wild type and complementing strain (rnr–/pHM1::rnr). Given these findings, we report for the first time that RNase R function is necessary for complete virulence of Xoo in rice. It is also important for motility of Xoo in media and for growth of Xoo at suboptimal temperature.
Oat Crown Rust Disease Severity Estimated at Many Time Points Using Multispectral Aerial Photos
Authors: McNish Ian G. , Smith Kevin P.
Published: August 2021

All plant breeding programs are dependent on plant phenotypic and genotypic data, but the development of phenotyping technology has been slow relative to that of genotyping. Crown rust (Puccinia coronata f. sp. avenae Erikss.) is the most important disease of cultivated oat (Avena sativa L.), making the development of disease-resistant oat cultivars an important breeding objective. Visual observation is the most common scoring method, but it can be laborious and subjective. We visually scored a diverse collection of 256 oat lines at a total of 27 time points in three disease nursery environments. Multispectral aerial photos were collected using an unmanned aerial vehicle at the same time points as the visual observations. The photos were analyzed, and subsets of the spectral properties of each plot were measured. Random forest modeling was used to model the relationship between the spectral properties of the plots and visually observed disease severity. The ability of the photo data and the random forest model to estimate visually observed disease severity was evaluated using three different cross-validation analyses. We specifically addressed the issue of assessing phenotyping accuracy across and within time points. The accuracy of the photo estimates was greatest for adult plants shortly before they began to senesce. Accuracy outside of that time frame was generally low but statistically significant. Unmanned aerial vehicle–mounted sensors could increase disease scoring efficiency, but additional investigation into the spectral signature of disease severity at all plant growth stages may be necessary to automate accurate full-season measurements.
The role of endocrine hormones in the pathogenesis of adolescent idiopathic scoliosis
Authors: Liang Zhuo‐Tao , Guo Chao‐Feng , Li Jiong , Zhang Hong‐Qi
Published: August 2021

Adolescent idiopathic scoliosis (AIS) is a common spinal deformity characterized by changes in the three‐dimensional structure of the spine. It usually initiates during puberty, the peak period of human growth when the secretion of numerous hormones is changing, and it is more common in females than in males. Accumulating evidence shows that the abnormal levels of many hormones including estrogen, melatonin, growth hormone, leptin, adiponectin and ghrelin, may be related to the occurrence and development of AIS. The purpose of this review is to provide a summary and critique of the research published on each hormone over the past 20 years, and to highlight areas for future study. It is hoped that the presentation will help provide a better understanding of the role of endocrine hormones in the pathogenesis of AIS.
Assessment of receptor affinities of ophthalmic and systemic agents in dry eye disease
Authors: Janeczko Patrick , Norris Matthew R. , Bielory Leonard
Published: August 2021

Purpose of review

To explore our current understanding of receptor profiles acted upon by medications used to treat dry eye disease (DED).

Recent findings

Research into histaminic and muscarinic receptor affinities for drugs targeting the ocular surface has not kept up with bench research pertaining to the receptor profile of the ocular surface. These insights are necessary for better evaluation of medications used in DED and other allergic disorders.

At the H1 receptor, Ketotifen (pKa = 9.2), pyrilamine (pKa = 9.0), and epinastine (pKa = 8.0) had the highest affinities, whereas ranitidine (pKa = 4.2) and cimetidine (pKa = 4.9) had the lowest. Ketotifen, a second-generation antihistamine, was found to have a pKa of 6.7 at muscarinic receptors which was higher than that of diphenhydramine (pKa = 6.4), a first-generation antihistamine. Additionally, second-generation antihistamines have higher affinity for H3 receptors, which have been linked to urticaria, compared to first-generation. Azelastine, a second-generation, demonstrated significant affinity (pKa = 7.1) at the H3 receptor compared to all other drugs. Antazoline (pKa = 4.4) and diphenhydramine (pKa = 4.6), both first-generation antihistamines, had the lowest affinities for the H3 receptor. These findings raise questions about the use of antihistamines in the treatment of DED and allergic disorders.
Comparison of structural components and functional mechanisms within the skin vs. the conjunctival surface
Authors: Valentine Lauren , Norris Matthew R. , Bielory Leonard
Published: August 2021

Purpose of review

The purpose of this review is to highlight and compare the structural and functional differences between the ocular surface and the skin. The goal is to further understand how these components interact from an immunobiological standpoint, which may inform future therapeutic uses.

Recent findings

Treatment agents, such as Dupilumab and Apremilast are traditionally indicated for integumentary conditions, such as atopic dermatitis and psoriasis, respectively. Both were also found to have potent effects on the conjunctival surface and ocular glands, which may be attributed to the similarities in structure.

Surfaces of the eyes and the skin are found to have similar composition in terms of immunohistology, steroidogenic properties, and allergic mechanisms. These translate directly into both the adverse effects and therapeutic benefits that overlap when treating these surfaces.
The Influence of Carbon Dioxide on Cerebral Autoregulation During Sevoflurane-based Anesthesia in Patients With Type 2 Diabetes
Authors: van den Dool Rokus E.C. , Immink Rogier V. , van der Ster Björn J.P. , Hermanides Jeroen , Hollmann Markus W. , Preckel Benedikt , van Lieshout Johannes J. , Sperna Weiland Nicolaas H.
Published: August 2021

Background:

Cerebral autoregulation (CA) continuously adjusts cerebrovascular resistance to maintain cerebral blood flow (CBF) constant despite changes in blood pressure. Also, CBF is proportional to changes in arterial carbon dioxide (CO2) (cerebrovascular CO2 reactivity). Hypercapnia elicits cerebral vasodilation that attenuates CA efficacy, while hypocapnia produces cerebral vasoconstriction that enhances CA efficacy. In this study, we quantified the influence of sevoflurane anesthesia on CO2 reactivity and the CA-CO2 relationship.

Methods:

We studied patients with type 2 diabetes mellitus (DM), prone to cerebrovascular disease, and compared them to control subjects. In 33 patients (19 DM, 14 control), end-tidal CO2, blood pressure, and CBF velocity were monitored awake and during sevoflurane-based anesthesia. CA, calculated with transfer function analysis assessing phase lead (degrees) between low-frequency oscillations in CBF velocity and mean arterial blood pressure, was quantified during hypocapnia, normocapnia, and hypercapnia.

Results:

In both control and DM patients, awake CO2 reactivity was smaller (2.8%/mm Hg CO2) than during sevoflurane anesthesia (3.9%/mm Hg; P<0.005). Hyperventilation increased CA efficacy more (3 deg./mm Hg CO2) in controls than in DM patients (1.8 deg./mm Hg CO2; P<0.001) in both awake and sevoflurane-anesthetized states.

Conclusions:

The CA-CO2 relationship is impaired in awake patients with type 2 DM. Sevoflurane-based anesthesia does not further impair this relationship. In patients with DM, hypocapnia induces cerebral vasoconstriction, but CA efficacy does not improve as observed in healthy subjects.
Perceived Racial Discrimination in the Pregnant African American Population
Authors: Mileski Megan R. , Shirey Maria R. , Patrician Patricia A. , Childs Gwendolyn
Published: August 2021

African American women experience higher lifetime exposure to chronic stressors, such as perceived racial discrimination. Clearly defining perceived racial discrimination in the pregnant African American population has the potential to better explain the phenomenon and how it relates to adverse birth outcomes such as preterm birth. The purpose of this concept analysis is to more clearly define perceived racial discrimination in the pregnant African American population using Rodgers' evolutionary method. Defining the concept of interest has the potential to uncover modifiers that may help close the gap in the Black-White infant mortality rates in the United States.
An Analysis of Online Ratings of Pediatric Orthopaedic Surgeons
Authors: Jay Jordan H. , Runge Nicholas E. , Vergara Franz H. , Sabatini Coleen S. , Oni Julius K.
Published: August 2021

Background:

Patients continue to utilize physician review websites (PRWs) to assist in their selection of a health care provider. Studies on PRWs and how they affect patient care have recently become popular in the literature. This study analyzes PRW ratings of a previously unexamined subspecialty, pediatric orthopaedic surgeons.

Methods:

Three hundred ninety-nine randomly selected Pediatric Orthopaedic Society of North America member’s PRW ratings were examined from May 4, 2020 to July 18, 2020. Healthgrades.com, Vitals.com, RateMDs.com, and Google.com were reviewed. Number of ratings and average ratings (0 to 5.0) were recorded. Provider sex, years in practice (0 to 10, 11 to 20, and 21+), practice type (academic, private), geographic location (Northeast, Southeast, Midwest, Southwest, West), degree (Medical Doctor, Doctor of Osteopathic Medicine), and fellowship training (yes, no) were recorded. Kruskal-Wallis testing was performed to determine factors affecting positive surgeon ratings.

Results:

98.5% (393) of Pediatric Orthopaedic Society of North America surgeons were rated on a PRW at least once and were highly rated with an average rating of 4.14 of 5.0. Surgeons in practice 1 to 10 years had higher ratings than those in practice 11 to 20 and 21+ years, on Healthgrades.com (P=0.049) and RateMDs.com (P=0.011). Academic surgeons were found to have higher ratings than those in private practice on Google.com (P=0.007). Sex, region of practice, degree type, and fellowship training status did not have an effect on online ratings across all PRWs.

Conclusions:

Pediatric orthopaedic surgeons are frequently and highly rated, similar to other orthopaedic subspecialties. Surgeons in practice 1 to 10 years were found to have statistically higher ratings on some websites. Academic surgeons were found to have statistically higher ratings on some websites.
Physeal Abnormalities in Children With High-risk Neuroblastoma Intensively Treated With/Without 13-Cis-Retinoic Acid
Authors: Koh Kyung-Nam , Jeon Ji Young , Park Soo-Sung , Im Ho Joon , Kim Hyery , Kang Michael Seungcheol
Published: August 2021

Background:

This study aimed to investigate the presence of physeal abnormality and its effect on growth in children with high-risk neuroblastoma treated by intensive multimodal treatment with/without 13-cis-retinoic acid (13-CRA).

Methods:

Fifteen patients diagnosed with high-risk neuroblastomas at the age of 1 to 10 years, who received treatment such as high-dose chemotherapy and autologous stem cell transplantation with/without 13-CRA, and with complete data during their >2-year follow-up were retrospectively reviewed. The physeal abnormalities were investigated by whole-body magnetic resonance imaging, serially performed every 3 to 6 months. The patients’ height growth was also investigated and compared with that of age-and-sex-matched patients with brain tumors who also underwent high-dose chemotherapy and autologous stem cell transplantation.

Results:

Six of 15 patients presented multifocal physeal abnormalities during follow-up, and all lesions occurred in patients with 13-CRA use. The lesions in 3 patients completely resolved spontaneously without any adverse effect on growth, but some lesions in the other 3 patients progressed to disturb the bony growth. Height growth of matched patients with brain tumors were not significantly different, and none of the matched controls showed definite bony deformity during the follow-up.

Conclusions:

Some children who were treated for high-risk neuroblastomas experienced multifocal physeal insults, probably due to the use of 13-CRA. Most lesions resolved spontaneously, but some led to bony deformity. If the lesions are not followed by premature physeal closure, there seems to be no further adverse effect of 13-CRA on leg length growth. Routine periodic screening for physeal status is needed for the patients with high-risk neuroblastomas using 13-CRA.

Level of Evidence:

Level IV—prognostic study.
Long-term survival in a patient with advanced lung adenocarcinoma harboring synchronous EGFR exon 18 G719A and BRAF V600E mutations and treated with afatinib: a case report
Authors: Huang Qing , Chen Changchun , Hu Sheng , Wu Huijing , Yu Ding , Zhu Xianmin , Xue Chang , Wu Yuebing , Tang Jing , Xie Rong , Ran Fengming
Published: August 2021

EGFR and BRAF V600E mutations are both early driven and usually mutually exclusive. We report the case of a 59-year-old woman diagnosed with advanced lung adenocarcinoma harboring coexisting EGFR exon 18 G719A and BRAF V600E mutations. She experienced a long-term response to oral afatinib, with a progression-free survival rate of 33 months and an overall survival rate of 11 years. Lung adenocarcinoma with synchronous EGFR G719A and BRAF V600E mutations is rare and has not been previously reported. This case highlights the importance of an adequate response to afatinib and provides an optimal therapeutic option for such patients.
Response to olaparib in metastatic lung adenocarcinoma with germline BRCA2 mutation: a case report
Authors: Wu Chao , Fan Mengjiao , Hu Yi
Published: August 2021

Mutation of BRCA2, a breast cancer susceptibility gene, is associated with the development of breast and ovarian cancer. Olaparib is an oral poly-adenosine diphosphate–ribose polymerase (PARP) inhibitor, which has been proven to treat BRCA-mutated tumors effectively, especially breast and ovarian cancer. Here, we report a case of a germline BRCA2-mutated metastatic lung adenocarcinoma, non–small-cell lung cancer, responded well to olaparib. A 41-year-old man with no history of smoking was diagnosed with advanced lung adenocarcinoma. The patient was treated with bevacizumab, pemetrexed disodium, and cis-platinum in the first-line therapy of 6 months, followed by bevacizumab, Abraxane, and sintilimab treatments for another 6 months. As disease progression was confirmed and the presence of germline BRCA2 mutation, the combinational treatment of olaparib/anlotinib was applied to achieve partial response 1 month later, and the progression-free survival was extended for another 5 months. This study shows metastatic lung adenocarcinoma with BRCA2 mutation could also respond well to PARP inhibitor, broadening the spectrum of BRCA-mutated cancers suitable for olaparib therapy. With acquired resistance to chemotherapy, bevacizumab, and immunotherapy, the patient still gained significant benefits from the targeted therapy.
Differential prognostic impact of complete blood count-related parameters by prior use of novel androgen receptor pathway inhibitors in docetaxel-treated castration-resistant prostate cancer patients
Authors: Kobayashi Hiroki , Shiota Masaki , Sato Nobuaki , Kobayashi Satoshi , Matsumoto Takashi , Monji Keisuke , Kashiwagi Eiji , Takeuchi Ario , Inokuchi Junichi , Shiga Ken-ichiro , Yokomizo Akira , Eto Masatoshi
Published: August 2021

There are multiple reports on the value of complete blood count (CBC)-related parameters on prognosis in docetaxel-treated castration-resistant prostate cancer (CRPC) patients before the emergence of androgen receptor pathway inhibitors (ARPIs). We investigated the prognostic significance of CBC-related parameters in docetaxel-treated CRPC patients. Patients treated with docetaxel chemotherapy for CRPC between 2008 and 2018 were included. We analyzed the relevance of CBC-related parameters to oncological prognosis in docetaxel chemotherapy, associated with prior use of novel ARPIs. Among 144 Japanese men treated with docetaxel, 49 men (34.0%) had already received ARPI therapy. A high neutrophil–lymphocyte ratio (NLR) was a prognostic factor for poor progression-free survival and overall survival (OS) in both univariate and multivariate analyses. In addition, a low hemoglobin (Hb) level and a high systemic immune-inflammation index (SII) were prognostic factors of poor OS in univariate analysis. Hb level was a prognostic factor of OS in both ARPI-naive and ARPI-treated patients. However, a high NLR and SII were only associated with a poor prognosis in ARPI-naive but not in ARPI-treated patients. Hb, NLR, and SII have been suggested to be prognosticators in docetaxel-treated CRPC patients. The differential prognostic value of NLR and SII between ARPI-naive and ARPI-treated patients may require caution when using these markers in docetaxel-treated CRPC patients.
Pazopanib-induced chylothorax in a patient with renal cell carcinoma
Authors: Koylu Bahadir , Tekin Fatih , Aktas Burak Yasin , Kilickap Saadettin , Koksal Deniz
Published: August 2021

Pazopanib is an oral multi-kinase inhibitor approved for the treatment of advanced renal cell carcinoma (RCC). It is an anti-angiogenic agent, which blocks the activation signaling pathways of tyrosine kinases and prevents the activities of primarily vascular endothelial growth factor receptors (VEGFR)-2 and VEGFR-3, which are important in lymphangiogenesis. Herein, we report a patient with advanced RCC who developed asymptomatic left-sided chylothorax under pazopanib therapy. Chylothorax developed in the 16th month and gradually increased until it was diagnosed by thoracentesis in the 22nd month. The development of chylothorax was attributed to pazopanib therapy after ruling out all possible traumatic and nontraumatic etiologies. The ‘Adverse Drug Reaction Probability Scale’ revealed a total score of 6, which fell into ‘probable’ category. Chylothorax regressed significantly 5 weeks after the discontinuation of pazopanib therapy.
Anlotinib is effective in the treatment of advanced pancreatic cancer: a case report
Authors: Li Shuyi , Niu Mengke , Deng Wenying , Li Ning , Wei Chen , Luo Suxia
Published: August 2021

Effective treatments are urgently needed for patients with advanced pancreatic cancer. Anlotinib is a novel small-molecule multitarget tyrosine kinase inhibitor with broad inhibitory effects on tumor growth and angiogenesis. Here, we present an advanced pancreatic cancer patient, who respond to anlotinib targeted therapy after the failure of multiline chemotherapy and apatinib targeted therapy. Anlotinib was given orally at a dose of 10 mg once daily (2 weeks on/1 week off), and progression-free survival was 5.6 months. The adverse reaction of anlotinib was elevated aminotransferase and fatigue, but it was tolerable and reversible. Our case indicates that anlotinib might be effective in the treatment of advanced pancreatic cancer. This case report may offer a new targeted treatment option for heavily treated advanced pancreatic cancer.
Kirsten rat sarcoma viral oncogene homolog G12C mutant advanced non-small-cell lung cancer treated with MEK1/2 inhibitor trametinib: a case report
Authors: Jiang Ya , Liu Xin , Lv Dong-Lai , Zhao Xi-Long
Published: August 2021

No targeted therapies are approved for non-small-cell lung cancer (NSCLC) with Kirsten rat sarcoma viral oncogene homolog (KRAS) mutation to date. Trametinib, a selective allosteric inhibitor of the MEK1/2, demonstrated debatable clinical activity in KRAS-mutant NSCLC. In this case, we present a recurrent advanced NSCLC with KRAS G12C mutation successfully treated with single-agent trametinib therapy. An 87-year-old man who underwent radiotherapy for the right lung adenocarcinoma was admitted to clinical oncology center for recurrent lesions in bilateral lungs. He was unwilling to perform second-line chemotherapy, but underwent molecular profiling and revealed the KRAS G12C mutation. The single-agent target therapy of trametinib showed clinical benefit without obvious toxicity. Furthermore, this report reviewed the previous date of the preclinical and clinical and summarized that KRAS G12C mutation may be more sensitive to the inhibition of mitogen-activated protein kinase kinase. This case advocates for routine screening of KRAS point mutations in the utility of precision medicine and suggests that treatment with trametinib in advanced NSCLC cases with KRAS G12C mutation is well tolerated and effective, especially for those very elderly or unsuitable for more aggressive chemotherapy.
Circular RNA circ-RNF121 contributes to cisplatin (DDP) resistance of non-small-cell lung cancer cells by regulating the miR-646/SOX4 axis
Authors: Liu Yongrui , Zhai Ruiren , Hu Siqin , Liu Jing
Published: August 2021

Chemo-resistance is considered a major obstacle in the clinical treatment of non-small-cell lung cancer (NSCLC). Circular RNA (circRNA) circ-RNF121 (hsa_circ_0023404) has been identified to be related to the cisplatin (DDP) resistance. However, the role and mechanism of circ-RNF121 in the DDP resistance in NSCLC are still unknown. Real-time quantitative PCR (RT-qPCR) was applied to detect the levels of circ-RNF121, microRNA-646 (miR-646) and SRY-related HMG box transcription factor 4 (SOX4). Cell viability, proliferation, apoptosis, migration, invasion and cell cycle progression were assessed by 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2-H-tetrazolium bromide (MTT), colony formation, flow cytometry, wound-healing, transwell and flow cytometry assays, severally. The binding relationship between miR-646 and circ-RNF121 or SOX4 was predicted by the circular RNA interactome or Target Scan Human7.2 and then verified by a dual-luciferase reporter and RNA immunoprecipitation (RIP) assays. SOX4 protein level was measured by western blot assay. The biological role of circ-RNF121 on NSCLC tumor growth and drug resistance was examined by the xenograft tumor model in vivo. Circ-RNF121 and SOX4 were increased, and miR-646 was declined in DDP-resistant NSCLC tissues and cells. Furthermore, the circ-RNF121 deficiency could enhance DDP sensitivity by inhibiting cell proliferation, migration, invasion, cell cycle progression and promoting apoptosis in DDP-resistant NSCLC cells in vitro. Mechanically, circ-RNF121 served as a sponge of miR-646 to increase SOX4 expression. Circ-RNF121 knockdown improved the drug sensitivity of NSCLC in vivo. Circ-RNF121 silencing could reduce the DDP resistance of NSCLC cells by regulating SOX4 expression via miR-646. These findings hinted at a promising therapeutic target for NSCLC treatment.
Fructose-1,6-bisphosphatase 2 represses cervical cancer progression via inhibiting aerobic glycolysis through promoting pyruvate kinase isozyme type M2 ubiquitination
Authors: Wang Bi , Yuan Yingnan , Zou Yin , Qi Zhengjun , Huang Guijia , Liu Yi , Xia Shan , Huang Yu , Huang Zhi
Published: August 2021

Growing evidence has shown that aerobic glycolysis, as a hallmark of cancer cells, plays a crucial role in cervical cancer. The aim of the study is to uncover whether fructose-1,6-bisphosphatase 2 (FBP2) is involved in cervical cancer progression via the aerobic glycolysis pathway. FBP2 levels were determined by quantitative PCR (qPCR) and western blotting. Cell growth viability and apoptosis were tested by cell counting kit-8 (CCK-8) and flow cytometry assays. Immunoprecipitation assay was applied for the detection of the FBP2 effect on pyruvate kinase isozyme type M2 (PKM2) ubiquitination. FBP2 level was decreased in cervical cancer, which is closely linked to shorter overall survival. FBP2 decreased cell growth and aerobic glycolysis and increased cell apoptosis, as well as decreased PKM2 expression and increased its ubiquitination level. The above-mentioned roles of FBP2 were weakened followed by PKM2 overexpression. FBP2 inhibited cervical cancer cell growth via inhibiting aerobic glycolysis by inducing PKM2 ubiquitination.
Clinical analysis of anlotinib as first-line treatment for elderly patients with advanced lung adenocarcinoma without driver gene mutations
Authors: Zhu Jinxiu , Xie Qiang , Zhong Aihong , Le Yuyin
Published: August 2021

This retrospective study was conducted to explore the effects of anlotinib as first-line treatment for patients with advanced lung adenocarcinoma. We retrospectively reviewed medical records of 60 patients with advanced lung adenocarcinoma, admitted to the Fuzhou Pulmonary Hospital between August 2018 and December 2019. We calculated and recorded the objective remission rate (ORR), disease control rate (DCR), adverse reactions, quality of life assessment, progression-free survival (PFS) and overall survival (OS) for each group. We applied χ2, Mann–Whitney U test, Kaplan–Meier and log-rank statistical methods as appropriate to analyze the data. We found no statistically significant differences in either ORR (17.5 vs. 15%) or DCR (67.5 vs. 65.5%) between the anlotinib and pemetrexed groups (P > 0.05). The adverse reactions graded ≥3 in the anlotinib group were fatigue and diarrhea and they accounted for 5% of all the adverse reactions in the group. The patients in the anlotinib group presented better physical, role, cognitive, emotional, and social functions than those in the pemetrexed group (P < 0.05). The symptoms of fatigue, nausea and vomiting, loss of appetite and constipation in the anlotinib group were significantly less frequent than those in the pemetrexed group (P < 0.05). We found similar median PFSs (3.0 vs. 2.8 months) and median OSs (7.0 vs. 7.0 months) in both treatment groups (P > 0.05). The choice of anlotinib as first-line chemotherapy for treating elderly patients with advanced lung adenocarcinoma was effective, safe; the treatment was better than other drugs at improving the patients’ quality of life.
Baseline left ventricular ejection fraction associated with symptom improvements in both children and adolescents with postural tachycardia syndrome under metoprolol therapy
Authors: Wang Yuan-Yuan , Han Zhen-Hui , Wang Yu-Li , Liao Ying , Zhang Chun-Yu , Liu Ping , Tang Chao-Shu , Du Jun-Bao , Jin Hong-Fang , Huang Ya-Qian
Published: August 2021

Background:

Postural tachycardia syndrome (POTS) is a common childhood disease that seriously affects the patient's physical and mental health. This study aimed to investigate whether pre-treatment baseline left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS) values were associated with symptom improvement after metoprolol therapy for children and adolescents with POTS.

Methods:

This retrospective study evaluated 51 children and adolescents with POTS who received metoprolol therapy at the Peking University First Hospital between November 2010 and July 2019. All patients had completed a standing test or basic head-up tilt test and cardiac echocardiography before treatment. Treatment response was evaluated 3 months after starting metoprolol therapy. The pre-treatment baseline LVEF and LVFS values were evaluated for correlations with decreases in the symptom score after treatment (ΔSS). Multivariable analysis was performed using factors with a P value of <0.100 in the univariate analyses and the demographic characteristics.

Results:

A comparison of responders and non-responders revealed no significant differences in demographic, hemodynamic characteristics, and urine specific gravity (all P > 0.050). However, responders had significantly higher baseline LVEF (71.09% ± 4.44% vs. 67.17% ± 4.88%, t = −2.789, P = 0.008) and LVFS values (40.00 [38.00, 42.00]% vs. 36.79% ± 4.11%, Z = −2.542, P = 0.010) than the non-responders. The baseline LVEF and LVFS were positively correlated with ΔSS (r = 0.378, P = 0.006; r = 0.363, P = 0.009), respectively. Logistic regression analysis revealed that LVEF was independently associated with the response to metoprolol therapy in children and adolescents with POTS (odds ratio: 1.201, 95% confidence interval: 1.039–1.387, P = 0.013).

Conclusions:

Pre-treatment baseline LVEF was associated with symptom improvement after metoprolol treatment for children and adolescents with POTS.
Drug Levels Associated With Optimal Discrimination Between Remission and Nonremission and Comparison of Antibody Assays During First Year of Stable Infliximab Maintenance Therapy in Inflammatory Bowel Disease
Authors: Dorn-Rasmussen Maria , Buhl Sine , Brynskov Jørn , Bay Jakob T. , Bolstad Nils , Klausen Tobias W. , Warren David J. , Ainsworth Mark A. , Steenholdt Casper
Published: August 2021

Background:

To implement therapeutic drug monitoring–based strategies for infliximab (IFX) in inflammatory bowel disease, the authors assessed IFX levels for optimal discrimination between remission and nonremission and compared assays for anti-IFX antibodies (Abs).

Methods:

The retrospective cohort comprised 163 bionaive patients with inflammatory bowel disease who received stable IFX maintenance therapy (5 mg/kg every 8 weeks [q8w]) for 1 year. The clinical and biochemical remission status was assessed at all infusions (weeks 14-22-30-38-46-54), and IFX and anti-IFX Abs were estimated using a time-resolved fluorometric assay (n = 690; 88% of infusions). Samples positive for anti-IFX Abs or IFX levels < limit of detection (n = 102) were analyzed by 2 binding assays [enzyme-linked immunosorbent assay (ELISA)] and functional reporter gene assay/drug-tolerant enzyme immunoassay.

Results:

At all assessed time points, IFX levels were more than double in patients presenting clinical or biochemical remission. An IFX concentration of 4.5 mcg/mL was associated with clinical remission during the entire first year of therapy [sensitivity 54% (49–59), specificity 73% (67–78), AUCROC 0.65 (0.60–0.69), P < 0.0001]; these values were comparable with biochemical remission. Exploratory assessments for endoscopic remission (n = 131) were performed at the discretion of the treating physician. Anti-IFX Abs were associated with undetectable IFX and treatment failure [OR 2.9 (1.4–6.0), P < 0.01], irrespective of persistency or transiency. All performed assays detected anti-IFX Abs were picked up by all assays in ∼2/3 of samples. Binding assays demonstrated a higher sensitivity to anti-IFX Abs.

Conclusions:

IFX at ∼5 mcg/mL was associated with clinical and biochemical remission during the first year of maintenance therapy. During this phase of therapy, standard binding assays are appropriate for therapeutic drug monitoring.
Clinical characteristics, practice patterns, and outcomes of patients with acute severe hypertension visiting the emergency department
Authors: Kim Byung Sik , Kim Hyun-Jin , Lyu Minhyung , Kim Wook-Dong , Lee Yonggu , Kim Miso , Lee Suein , Park Jin-Kyu , Shin Jinho , Shin Hyungoo , Kim Changsun , Shin Jeong-Hun
Published: August 2021

Objectives:

Data regarding acute severe hypertension, a life-threatening condition encountered in the emergency department, are limited. We aimed to identify the characteristics, practice patterns, and outcomes of patients with acute severe hypertension in the emergency department.

Methods:

This cross-sectional study at a tertiary referral centre included patients aged at least 18 years who were admitted to the emergency department between January 2016 and December 2019 for acute severe hypertension, which was defined as SBP at least 180 mmHg and/or DBP at least 100 mmHg.

Results:

Of 172 105 patients who visited the emergency department, 10 219 (5.9%) had acute severe hypertension. Of them, 2506 (24.5%) patients had acute hypertension-mediated organ damage (HMOD), and these patients had more cardiovascular risk factors than did patients without HMOD. Additionally, 4137 (40.5%) patients were admitted, and nine (0.1%) died in the emergency department. The overall 3-month, 1-year, and 3-year mortality rates were 4.8, 8.8, and 13.9%, respectively. In patients with HMOD, the 1-year mortality rate was 26.9%, and patients lost to follow-up had a significantly higher 1-year mortality rate than those who were followed up (21.3 vs. 10.5%, respectively, P < 0.001).

Conclusion:

The mortality rate in patients with acute severe hypertension in the emergency department is high, especially in patients with HMOD. Evaluation of HMOD, investigating the underlying causes, and adequate follow-up are mandatory to improve the outcomes in these patients. This study emphasizes the need for disease-specific guidelines that include detailed acute treatment strategies and follow-up management for acute severe hypertension.
Advanced imaging tools for evaluating cardiac morphological and functional impairment in hypertensive disease
Authors: Lembo Maria , Manzi Maria Virginia , Mancusi Costantino , Morisco Carmine , Rao Maria Assunta Elena , Cuocolo Alberto , Izzo Raffaele , Trimarco Bruno
Published: August 2021

Arterial hypertension represents a systemic burden, and it is responsible of various morphological, functional and tissue modifications affecting the heart and the cardiovascular system. Advanced imaging techniques, such as speckle tracking and three-dimensional echocardiography, cardiac magnetic resonance, computed tomography and PET-computed tomography, are able to identify cardiovascular injury at different stages of arterial hypertension, from subclinical alterations and overt organ damage to possible complications related to pressure overload, thus giving a precious contribution for guiding timely and appropriate management and therapy, in order to improve diagnostic accuracy and prevent disease progression. The present review focuses on the peculiarity of different advanced imaging tools to provide information about different and multiple morphological and functional aspects involved in hypertensive cardiovascular injury. This evaluation emphasizes the usefulness of the emerging multiimaging approach for a comprehensive overview of arterial hypertension induced cardiovascular damage.
Independent relationships between renal mechanisms and systemic flow, but not resistance to flow in primary hypertension in Africa
Authors: Malan Nico , Norton Gavin R. , Peterson Vernice R. , Yusuf Suraj M. , Libhaber Elena , Libhaber Carlos D. , Mmopi Keneilwe N. , Bello Hamza , Masiu Mohlabani , Da Silva Fernandes Daniel , Tade Grace , Mthembu Nonhlanhla , Peters Ferande , Dessein Patrick H. , Sareli Pinhas , Woodiwiss Angela J.
Published: August 2021

Aims:

Whether renal mechanisms of hypertension primarily translate into increases in systemic vascular resistance (SVR) in all populations is uncertain. We determined whether renal mechanisms associate with either increases in SVR (and impedance to flow) or systemic flow in a community of African ancestry.

Method:

In a South African community sampled across the full adult age range (n = 546), we assessed stroke volume (SV), peak aortic flow (Q), SVR, characteristic impedance (Zc) and total arterial compliance (TAC) from velocity and diameter measurements in the outflow tract (echocardiography) and central arterial pressures. Renal changes were determined from creatinine clearance (glomerular filtration rate, GFR) and fractional Na+ excretion (FeNa+) (derived from 24-h urine collections).

Results:

Independent of confounders (including MAP and pressures generated by the product of Q and Zc), SV (and hence cardiac output) (P < 0.0001) and Q (P < 0.01), but not SVR, Zc or TAC (P = 0.09–0.20) were independently associated with decreases in both GFR (index of nephron number) and FeNa+. Through an interactive effect (P < 0.0001), the impact of GFR on SV or Q was strongly determined by FeNa+ and vice versa. The relationship between the GFR-FeNa+ interaction and either SV or Q was noted in those above or below 50 years of age, although neither GFR, FeNa+ nor the interaction were independently associated with SVR, Zc or TAC at any age.

Conclusion:

Across the full adult lifespan, in groups of African ancestry, renal mechanisms of hypertension translate into increases in systemic flow rather than into resistance or impedance to flow.
EVALUATION OF ARTIFICIAL INTELLIGENCE–BASED QUANTITATIVE ANALYSIS TO IDENTIFY CLINICALLY SIGNIFICANT SEVERE RETINOPATHY OF PREMATURITY
Authors: Li Jie , Huang Kaide , Ju Rong , Chen Yuanyuan , Li Mengyu , Yang Shijun , Wang Yue , Dong Wentao , Liu Miao , Chen Sizhu , Leng Hongmei , Zhong Jie
Published: August 2021

Purpose:

To evaluate the screening potential of a deep learning algorithm–derived severity score by determining its ability to detect clinically significant severe retinopathy of prematurity (ROP).

Methods:

Fundus photographs were collected, and standard panel diagnosis was generated for each examination by combining three independent image-based gradings. All images were analyzed using a deep learning algorithm, and a quantitative assessment of retinal vascular abnormality (DeepROP score) was assigned on a 1 to 100 scale. The area under the receiver operating curve and distribution pattern of all diagnostic parameters and categories of ROP were analyzed. The correlation between the DeepROP score and expert rank ordering according to overall ROP severity of 50 examinations was calculated.

Results:

A total of 9,882 individual examinations with 54,626 images from 2,801 infants were analyzed. Fifty-six examinations (0.6%) demonstrated Type 1 ROP and 54 examinations (0.5%) demonstrated Type 2 ROP. The DeepROP score had an area under the receiver operating curve of 0.981 for detecting Type 1 ROP and 0.986 for Type 2 ROP. There was a statistically significant correlation between the expert rank ordering of overall disease severity and the DeepROP score (correlation coefficient 0.758, P < 0.001). When hypothetical referral cutoff score of 35 was selected, all cases of severe ROP (Type 1 and Type 2 ROP) was captured and 8,562 eyes (87.6%) with no or mild ROP were excluded.

Conclusion:

The DeepROP score determined by deep learning algorithm was an objective and quantitative indicator for the severity of ROP, and it had potential in automated detecting clinically significant severe ROP.
Lower Cognitive Function in Patients With Functionally and Structurally Severe Glaucoma: The LIGHT Study
Authors: Yoshikawa Tadanobu , Obayashi Kenji , Miyata Kimie , Saeki Keigo , Ogata Nahoko
Published: August 2021

Precis:

This cross-sectional study of 172 patients with glaucoma showed that functional and structural glaucoma damage was significantly associated with cognitive impairment independent of age and visual acuity.

Purpose:

The aim of this study was to determine whether functional and structural glaucoma damage is associated with cognitive function.

Patients and Methods:

This was a cross-sectional analysis comprising 172 patients with glaucoma with a mean age of 70.6 years. Functional glaucoma severity was evaluated according to the visual field mean deviation (MD) (severe, MD ≤−12 dB; mild, MD >−12 dB), and structural glaucoma severity was determined based on circumpapillary retinal nerve fiber layer thickness. The main outcome measure was cognitive impairment defined by a Mini-Mental State Examination (MMSE) score of ≤26 and MMSE-blind score of ≤16.

Results:

The prevalence of patients with cognitive impairment (MMSE score ≤26) was significantly higher in the severe glaucoma group than in the mild glaucoma group (33.3% vs. 15.7%; P=0.010, respectively). Similar results were obtained in the analyses with MMSE-blind score of ≤16 (14.7% vs. 1.4%; P=0.003, respectively). Multivariable logistic regression analysis adjusted for potential confounders, including age, body mass index, education, visual acuity, hypertension, diabetes, and depressive symptoms, indicated a higher odds ratio (OR) for cognitive impairment (MMSE score ≤26) in patients with severe glaucoma than in those with mild glaucoma (OR, 2.62; 95% confidence interval, 1.006-6.84; P=0.049) and in relation to a 10-μm thinning of the retinal nerve fiber layer (OR, 1.42; 95% confidence interval, 1.05-1.93; P=0.025).

Conclusion:

Functional and structural glaucoma damage was significantly associated with lower cognitive function independent of age and visual acuity in a glaucoma cohort.
Pediatric Household Transmission of Severe Acute Respiratory Coronavirus-2 Infection—Los Angeles County, December 2020 to February 2021
Authors: Liu Patrick Y. , Gragnani Candace M. , Timmerman Jason , Newhouse Caitlin N. , Soto Gabriela , Lopez Lizzet , Spronz Rachel , Mhaskar Aditi , Yeganeh Nava , Fernandes Priyanka , Kuo Alice A.
Published: August 2021

This brief report presents transmission rates from a prospective study of 15 households with pediatric index cases of severe acute respiratory coronavirus-2 in Los Angeles County from December 2020 to February 2021. Our findings support ongoing evidence that transmission from pediatric index cases to household contacts is frequent but can be mitigated with practicing well-documented control measures at home, including isolation, masking and good hand hygiene.
Performance in Real World- and Virtual Reality-Based Spatial Navigation Tasks in Patients With Vestibular Dysfunction
Authors: Biju Kevin , Wei Eric X. , Rebello Elliott , Matthews Jacob , He Qiliang , McNamara Timothy P. , Agrawal Yuri
Published: August 2021

Objective:

This study evaluated whether vestibular dysfunction is associated with reduced spatial navigation performance.

Study Design:

Cross-sectional study.

Setting:

Otolaryngology Clinic in the Johns Hopkins Outpatient Center and an analogous virtual reality (VR) environment.

Patients:

Eligible patients had diagnosis of unilateral or bilateral vestibular loss. Matched healthy controls were recruited at 1:1 ratio.

Interventions:

The navigation task involved a route-based or place-based strategy in both real world and VR environments.

Main Outcome Measures:

Navigation performance was measured by distance travelled relative to optimal distance (i.e., path ratio) and the Judgments of Relative Direction (JRD) task, whereby participants had to recall relative angular distances between landmarks.

Results:

The study sample included 20 patients with vestibular loss (mean age: 61 yrs, SD: 10.2 yrs) and 20 matched controls (mean age: 60 yrs, SD: 10.4 yrs). Patients with vestibular loss travelled significantly greater distance using both route-based (path ratio 1.3 vs. 1.0, p = 0.02) and place-based (path ratio 2.6 vs. 2.0, p = 0.03) strategies in the real world. Overall, participants performed worse in virtual reality compared to real world in both path ratio (2.2 vs. 1.7; p = 0.04) and JRD error (78° vs. 67°; p < 0.01). Furthermore, while controls exhibited significant positive correlations between real world and VR performance in place-based (β = 0.75; p < 0.001) and JRD tasks (β = 0.70; p < 0.001), patients with vestibular loss exhibited no similar correlations.

Conclusions:

The vestibular system appears to play a role in navigation ability during both actual and virtual navigation, suggesting a role for static vestibular signals in navigation performance.
Four-Hour Delayed Gadolinium-Enhanced 3D-FLAIR MR Imaging Highlights Intralabyrinthine Micro-Schwannomas
Authors: Kurata Natsuko , Kawashima Yoshiyuki , Ito Taku , Ooka Tomoki , Tsutsumi Takeshi
Published: August 2021

Objective:

To demonstrate the clinical significance of 4-hour delayed gadolinium-enhanced three-dimensional fluid-attenuated inversion recovery (delayed 3D-FLAIR) in patients with intralabyrinthine schwannoma (ILS).

Patients:

Three patients who were clinically diagnosed with ILS.

Interventions:

All patients underwent audiological examinations and magnetic resonance imaging (MRI) scans. The MR-protocol included axial MR cisternography, immediate gadolinium-enhanced T1-weighted sequence, and heavily T2-weighted 3D-FLAIR prior to and 4 hours after the intravenous administration of gadolinium contrast medium.

Main Outcome Measures:

All MR images were visually inspected.

Results:

In all three patients with ILS, delayed 3D-FLAIR MRI demonstrated a strong signal of cochlear fluid surrounding the tumor, which highlighted a tumor region that lacked signals.

Conclusions:

Delayed 3D-FLAIR MRI may serve as a novel diagnostic tool for the early detection of intralabyrinthine micro-schwannoma. The findings also shed light on the pathophysiology of ILS.