bluuebunny/crossref_metadata_2025 huggingface dataset:
Blocking Rice Shoot Gravitropism by Altering One Amino Acid in LAZY1
Authors: Chen Shuifu , Huang Yuqun , Han Jingluan , Zhang Shijuan , Yang Qiaoyu , Li Zhijie , Zhang Ya , Mao Runyuan , Fan Ling , Liu Yaoguang , Chen Yuanling , Xie Xianrong
Published: August 2022

Tiller angle is an important trait that determines plant architecture and yield in cereal crops. Tiller angle is partially controlled during gravistimulation by the dynamic re-allocation of LAZY1 (LA1) protein between the nucleus and plasma membrane, but the underlying mechanism remains unclear. In this study, we identified and characterized a new allele of LA1 based on analysis of a rice (Oryza sativa L.) spreading-tiller mutant la1G74V, which harbors a non-synonymous mutation in the predicted transmembrane (TM) domain-encoding region of this gene. The mutation causes complete loss of shoot gravitropism, leading to prostrate growth of plants. Our results showed that LA1 localizes not only to the nucleus and plasma membrane but also to the endoplasmic reticulum. Removal of the TM domain in LA1 showed spreading-tiller phenotype of plants similar to la1G74V but did not affect the plasma membrane localization; thus, making it distinct from its ortholog ZmLA1 in Zea mays. Therefore, we propose that the TM domain is indispensable for the biological function of LA1, but this domain does not determine the localization of the protein to the plasma membrane. Our study provides new insights into the LA1-mediated regulation of shoot gravitropism.
The MdAux/IAA2 Transcription Repressor Regulates Cell and Fruit Size in Apple Fruit
Authors: Bu Haidong , Sun Xiaohuan , Yue Pengtao , Qiao Junling , Sun Jiamao , Wang Aide , Yuan Hui , Yu Wenquan
Published: August 2022

Auxin plays an important role in regulating plant development, and Auxin/indole acetic acid (Aux/IAA) is a type of auxin-responsive gene and plays an important role in auxin signaling; to date, although 29 Aux/IAA proteins have been reported in Abrabidopsis thaliana, only parts of the Aux/IAA family gene functions have been identified. We previously reported that a bud sport of ‘Longfeng’ (LF) apple (Malus domestica), named ‘Grand longfeng’ (GLF), which showed a larger fruit size than LF, has lower expression of MdAux/IAA2. In this study, we identified the function of the MdAux/IAA2 gene in apple fruit size difference using Agrobacterium-mediated genetic transformation. Overexpression of MdAux/IAA2 decreased the apple flesh callus increment and caused a smaller globular cell size. In addition, overexpression of MdAux/IAA2 in GLF fruit resulted in the reduction of apple fruit size, weight, and cell size, while silencing MdAux/IAA2 in LF apple fruit resulted in an increase in apple fruit weight and cell size. We suggest that the high auxin content depressed the expression of MdAux/IAA2, and that the downregulated expression of MdAux/IAA2 led to the formation of GLF. Our study suggests a mechanism for fruit size regulation in plants and we will explore the transcription factors functioning in this process in the future.
Development of Comprehensive Serological Techniques for Sensitive, Quantitative and Rapid Detection of Soybean mosaic virus
Authors: Ren Rui , Wang Tao , Gao Le , Song Puwen , Yang Yunhua , Zhi Haijian , Li Kai
Published: August 2022

Soybean is an important grain and oil crop worldwide; however, the yield and seed quality of which are seriously affected by Soybean mosaic virus (SMV). As efficient detection technology is crucial for the field management of SMV, novel immunological detection methods were developed in the present study. According to the phylogenetic analysis, the CP coding sequence of SMV-SC7 was selected for the prokaryotic expression of the recombinant SMV-CP. Purified SMV-CP was used for the development of polyclonal antibodies (PAb) against the SMV-CP (PAb-SMV-CP) and monoclonal antibodies (MAb) against SMV-CP (MAb-SMV-CP). Subsequently, the PAb-SMV-CP was used for the development of a novel DAS- quantitative ELISA (DAS-qELISA) kit, of which the sensitivity was greater than 1:4000, and this could be used for the quantitative detection of SMV in China. Meanwhile, the MAb-SMV-CP was labeled with colloidal gold, and then was used for the development of the SMV-specific gold immunochromatography strip (SMV-GICS). The SMV-GICS gives accurate detection results through observed control lines and test lines in 5 to 10 min, sharing the same sensitivity as RT-PCR, and can be used for rapid, accurate and high-throughput field SMV detection. The DAS-qELISA kit and the SMV-GICA strip developed in this study are SMV-specific, sensitive, cheap and easy to use. These products will be conducive to the timely, efficient SMV epidemiology and detection in major soybean-producing regions in China and abroad.
Toxic and Phenotypic Effects of AAV_Cre Used to Transduce Mesencephalic Dopaminergic Neurons
Authors: Erben Larissa , Welday Jacqueline P. , Murphy Ricardo , Buonanno Andres
Published: August 2022

A popular approach to spatiotemporally target genes using the loxP/Cre recombination system is stereotaxic microinjection of adeno-associated virus (AAV) expressing Cre recombinase (AAV_Cre) in specific neuronal structures. Here, we report that AAV_Cre microinjection in the ventral tegmental area (VTA) of ErbB4 Cyt-1-floxed (ErbB4 Cyt-1fl/fl) mice at titers commonly used in the literature (~1012–1013 GC/mL) can have neurotoxic effects on dopaminergic neurons and elicit behavioral abnormalities. However, these effects of AAV_Cre microinjection are independent of ErbB4 Cyt-1 recombination because they are also observed in microinjected wild-type (WT) controls. Mice microinjected with AAV_Cre (1012–1013 GC/mL) exhibit reductions of tyrosine hydroxylase (TH) and dopamine transporter (DAT) expression, loss of dopaminergic neurons, and they behaviorally become hyperactive, fail to habituate in the open field and exhibit sensorimotor gating deficits compared to controls microinjected with AAV_GFP. Importantly, these AAV_Cre non-specific effects are: (1) independent of serotype, (2) occur with vectors expressing either Cre or Cre-GFP fusion protein and (3) preventable by reducing viral titers by 1000-fold (1010 GC/mL), which retains sufficient recombination activity to target floxed genes. Our studies emphasize the importance of including AAV_Cre-injected WT controls in experiments because recombination-independent effects on gene expression, neurotoxicity and behaviors could be erroneously attributed to consequences of gene ablation.
Current Status of the Diagnosis and Management of Osteoporosis
Authors: Aibar-Almazán Agustín , Voltes-Martínez Ana , Castellote-Caballero Yolanda , Afanador-Restrepo Diego Fernando , Carcelén-Fraile María del Carmen , López-Ruiz Elena
Published: August 2022

Osteoporosis has been defined as the silent disease of the 21st century, becoming a public health risk due to its severity, chronicity and progression and affecting mainly postmenopausal women and older adults. Osteoporosis is characterized by an imbalance between bone resorption and bone production. It is diagnosed through different methods such as bone densitometry and dual X-rays. The treatment of this pathology focuses on different aspects. On the one hand, pharmacological treatments are characterized by the use of anti-resorptive drugs, as well as emerging regenerative medicine treatments such as cell therapies and the use of bioactive hydrogels. On the other hand, non-pharmacological treatments are associated with lifestyle habits that should be incorporated, such as physical activity, diet and the cessation of harmful habits such as a high consumption of alcohol or smoking. This review seeks to provide an overview of the theoretical basis in relation to bone biology, the existing methods for diagnosis and the treatments of osteoporosis, including the development of new strategies.
Functional Characterization of Serum Amyloid P Component (SAP) in Host Defense against Bacterial Infection in a Primary Vertebrate
Authors: Li Jiadong , Bai Hao , Yin Xiaoxue , Wu Zhelin , Qiu Li , Wei Xiayi , Zeng Qingliang , Mu Liangliang , Ye Jianmin
Published: August 2022

Serum amyloid P component (SAP), an ancient short pentraxin of the pentraxin family, plays an essential role in resistance to bacterial infection. In this study, the expression and functional characterization of SAP (OnSAP) in Nile tilapia (Oreochromis niloticus), a primary vertebrate, are investigated. The open reading frame of OnSAP is 645 bp of a nucleotide sequence encoding a polypeptide of 214 amino acids. As a calcium-binding protein, the structure and relative motif of OnSAP is highly similar to those of humans, containing amino acid residues Asn, Glu, Gln and Asp. In healthy fish, OnSAP mRNA is extensively distributed in all eleven tissues examined, with the highest level in spleen. The mRNA expression of OnSAP was significantly up-regulated after being challenged with gram-positive bacterium Streptococcus agalactiae and gram-negative bacterium Aeromonas hydrophila in vivo. In addition, recombinant OnSAP ((r)OnSAP) protein had capacities of binding S. agalactiae or A. hydrophila in the presence of Ca2+. Further, (r)OnSAP helped monocytes/macrophages to efficiently phagocytize bacteria. Moreover, the (r)OnSAP was able to enhance the complement-mediated lysis of the chicken red blood cells. Collectively, the evidence of SAP in tilapia, based on the results including its evolutionary conserved protein structure, bacterial binding and agglutination, opsonophagocytosis of macrophage and hemolysis enhancement, enriches a better understanding of the biological functions of the pentraxin family.
Vaccine for Diabetes—Where Do We Stand?
Authors: Chellappan Dinesh Kumar , Bhandare Richie R. , Shaik Afzal B. , Prasad Krishna , Suhaimi Nurfatihah Azlyna Ahmad , Yap Wei Sheng , Das Arpita , Banerjee Pradipta , Ghosh Nandini , Guith Tanner , Das Amitava , Balakrishnan Sarannya , Candasamy Mayuren , Mayuren Jayashree , Palaniveloo Kishneth , Gupta Gaurav , Singh Sachin Kumar , Dua Kamal
Published: August 2022

Diabetes is an endocrinological disorder with a rapidly increasing number of patients globally. Over the last few years, the alarming status of diabetes has become a pivotal factor pertaining to morbidity and mortality among the youth as well as middle-aged people. Current developments in our understanding related to autoimmune responses leading to diabetes have developed a cause for concern in the prospective usage of immunomodulatory agents to prevent diabetes. The mechanism of action of vaccines varies greatly, such as removing autoreactive T cells and inhibiting the interactions between immune cells. Currently, most developed diabetes vaccines have been tested in animal models, while only a few human trials have been completed with positive outcomes. In this review, we investigate the undergoing clinical trial studies for the development of a prototype diabetes vaccine.
Entity Linking Method for Chinese Short Text Based on Siamese-Like Network
Authors: Zhang Yang , Liu Jin , Huang Bo , Chen Bei
Published: August 2022

Entity linking plays a fundamental role in knowledge engineering and data mining and is the basis of various downstream applications such as content analysis, relationship extraction, question and answer. Most existing entity linking models rely on sufficient context for disambiguation but do not work well for concise and sparse short texts. In addition, most of the methods use pre-training models to directly calculate the similarity between the entity text to be disambiguated and the candidate entity text, and do not dig deeper into the relationship between them. This article proposes an entity linking method for Chinese short texts based on Siamese-like networks to address the above shortcomings. In the entity disambiguation task, the features of the Siamese-like network are used to deeply parse the semantic relationships in the text and make full use of the feature information of the entity text to be disambiguated, capturing the interdependent features within the sentences through an attention mechanism, aiming to find out the most critical elements in the entity text description. The experimental demonstration on the CCKS2019 dataset shows that the F1 value of the method reaches 87.29%, increase of 11.02% compared to the F1 value(that) of the baseline method, fully validating the superiority of the model.
One Species, Hundreds of Subspecies? New Insight into the Intraspecific Classification of the Old World Swallowtail (Papilio machaon Linnaeus, 1758) Based on Two Mitochondrial DNA Markers
Authors: Domagała Paweł J. , Lis Jerzy A.
Published: August 2022

The Old World swallowtail Papilio machaon Linnaeus, 1758 is one of the most well-known and most characteristic members of the family Papilionidae. Over the past two centuries, the butterfly has been the subject of many studies. P. machaon is characterised by a tendency to change the wing colour pattern. In turn, due to the great interest of collectors and amateur entomologists, these studies have been converted into the description of over 100 colour forms, aberrations and subspecies. In this study, mitochondrial DNA (mtDNA), 16S rDNA and cytochrome b sequences were used to examine the correlation between the intraspecific classification and genetic structure of P. machaon. The study used 87 specimens from 59 different localities covering the geographic distribution of this species in the Palaearctic. The phylogenetic relationships within and between the Old World swallowtail subspecies showed that the intraspecific classification proposed by various authors does not correlate with the variability in mitochondrial DNA sequences. In addition, populations occurring at the species distribution borders in the Palaearctic Region (i.e., Japan, Kamchatka, Morocco and Sakhalin) are genetically distinct from other species.
An Evaluation of Psychological Well-Being among Physicians and Nurses in Makkah’s Major Hospitals
Authors: Alghamdi Huda , Almalki Abdullah , Alshaikh Maha
Published: August 2022

Background: Physicians and nurses experience poor psychological well-being relative to other employees in healthcare fields. This study aimed to evaluate the psychological well-being among physicians and nurses in Makkah’s major hospitals. Methods: In this cross-sectional study, 460 physicians and nurses from seven major hospitals in Makkah were recruited to investigate their psychological well-being using the General Health Questionnaire-12 (GHQ-12) based on social dysfunction, anxiety, and confidence loss. Results: Over half (64.3%) of the physicians and nurses in this study scored at or above the GHQ-12 cut-off point (12), which is a positive result for poor psychological well-being. There were significant differences in the psychological well-being mean between Saudis and non-Saudis (t = 2.203, p = 0.028), years of work experience (t = 3.349, p = 0.001), hospitals (F = 2.848, p = 0.010), attending psychological support sessions (t = 2.082, p = 0.038), and history of visiting psychological clinics (t = −4.949, p < 0.001). There was also a significant association between the three GHQ-12 factors and the participants’ socio-demographic characteristics. Conclusion: The psychological well-being of physicians and nurses is low. The alarming number of physicians and nurses suffering from social dysfunction, anxiety, and loss of confidence should be addressed in Makkah’s major hospitals. The employee assistance program (EAP) could be highly valuable and effective for addressing the well-being of employees and their personal problems that may impact their work performance, conduct, health, and overall well-being at the Ministry of Health.
Inflammatory Bowel Disease Guidelines for Corneal Refractive Surgery Evaluation
Authors: Moshirfar Majid , Fuhriman David A. , Ali Amir , Odayar Varshini , Ronquillo Yasmyne C. , Hoopes Phillip C.
Published: August 2022

Inflammatory bowel disease (IBD) is a chronic systemic inflammatory condition that can potentially adversely affect surgical outcomes in patients receiving elective ophthalmic procedures. In this case series, 21 eyes of 11 patients with ulcerative colitis or Crohn’s disease underwent laser in situ keratomileusis (LASIK), photorefractive keratectomy (PRK), or small incision lenticule extraction (SMILE). Their surgical outcomes were followed up for an average of 8.9 ± 4.6 months. All the patients in this study did well, with 100% of eyes corrected for distance vision achieving uncorrected distance visual acuity 20/20 by postoperative month three. Common symptoms noted during the postoperative period included dry eyes, irritation, foreign body sensation, and blurry vision, all of which improved in prevalence and severity over the follow-up period, and none of the patients experienced a flare-up of their disease. Despite the successful outcomes in these patients, the authors recognize the inherent risks of operating on patients with IBD. Currently, there are no consensus guidelines for clinicians to follow to ensure that they are adequately screening these patients for eligibility, so the authors are suggesting a relevant, focused review of systems, a brief IBD history-related questionnaire, and a preliminary surgical decision-making flowchart for use in surgical evaluation.
Clinical Score for Predicting the Risk of Poor Ambulation at Discharge in Fragility Femoral Neck Fracture Patients: A Development Study
Authors: Tangchitphisut Paween , Khorana Jiraporn , Patumanond Jayanton , Rojanasthien Sattaya , Apivatthakakul Theerachai , Phinyo Phichayut
Published: August 2022

Surgical treatment in patients with fragility femoral neck fractures often leads to a longer length of hospital stay (LOS) and higher costs. Intensive rehabilitation is one of the choices to reduce LOS, but patient selection criteria are controversial. We intended to develop a clinical score to predict the risk of poor ambulation at discharge. This study was based on a retrospective cohort of patients diagnosed with fragility femoral neck fractures surgically managed from January 2010 to December 2019 at Chiang Mai University (CMU) Hospital. Pre-, intra-, and post-operative factors that affect rehabilitation training were candidate predictors. All patients were categorized into able or unable groups based on their ability to bear self-weight at discharge. Logistic regression was used for score derivation. Five hundred and nine patients were included in this study. Male sex, end-stage kidney disease (ESRD), cerebrovascular disease, psychiatric disorders, pre-fracture ambulation with gait aids, concomitant fracture, post-operative intensive care unit (ICU) admission or ventilator use, and urinary catheter use at second day post-operation were identified as the prognostic factors. The score showed an AuROC of 0.84 with good calibration. The score can be used for risk stratification on the second day post-operation. External validation is encouraged before clinical implementation.
The Combining of Tyrosine Kinase Inhibitors and Immune Checkpoint Inhibitors as First-Line Treatment for Advanced Stage Hepatocellular Carcinoma
Authors: Lee Shou-Wu , Yang Sheng-Shun , Lien Han-Chung , Peng Yen-Chun , Tung Chun-Fang , Lee Teng-Yu
Published: August 2022

Aim: Hepatocellular carcinoma (HCC) is one of the most common cancers. Tyrosine kinase inhibitors (TKIs), including sorafenib (SOR) and lenvatinib (LEN), as well as immune checkpoint inhibitors (ICIs), including nivolumab (NIVO) and pembrolizumab (PEMBRO), have been approved for the treatment of advanced HCC. The aim of the study is to determine whether advanced-stage HCC patients should receive a combination of TKI and ICI as first-line therapy. Methods: Data for subjects with BCLC stage C HCC, who were receiving combining TKI and ICI as first-line therapy at Taichung Veterans General Hospital from April 2019 to July 2021, were evaluated. The general and therapeutic outcome data were collected and analyzed. Results: A total of 33 patients were enrolled (8 SOR/NIVO, 4 SOR/PEMBRO, 11 LEN/NIVO, and 10 LEN/PEMBRO). All cases belonged to Child-Pugh class A. The objective response rate was 48.5%, and disease control rate was 72.7%. The average progression-free survival (PFS) and overall survival (OS) of all patients was 9.2 and 17.0 months, respectively. The use of PEMBRO, when compared with NIVO, had a significantly positive impact towards achieving an objective response, defined as either complete response or partial response (OR 5.54, p = 0.045). PFS and OS between the different TKIs or ICIs had no differences. The most adverse event was fatigue (36.4%), and most cases were mild and manageable. Conclusion: Combining TKI and ICI provides an acceptable antitumor efficacy in first-line therapy for advanced-stage HCC patients. The survival outcomes between different TKIs or ICIs display no differences.
Donor Site Morbidity and Quality of Life after Microvascular Head and Neck Reconstruction with a Chimeric, Thoracodorsal, Perforator-Scapular Flap Based on the Angular Artery (TDAP-Scap-aa Flap)
Authors: Wallner Jürgen , Rieder Marcus , Schwaiger Michael , Remschmidt Bernhard , Zemann Wolfgang , Pau Mauro
Published: August 2022

Extensive defects in the head and neck area often require the use of advanced free flap reconstruction techniques. In this study, the thoracodorsal perforator-scapular free flap technique based on the angular artery (TDAP-Scap-aa flap) was postoperatively evaluated regarding the quality of life and the donor site morbidity using the standardized SF-36 and DASH questionnaires (short form health 36 and disabilities of the arm, shoulder and hand scores). Over a five-year period (2016–2020), 20 selected cases (n = 20) requiring both soft and hard tissue reconstruction were assessed. On average, the harvested microvascular free flaps consisted of 7.8 ± 2.1 cm hard tissue and 86 ± 49.8 cm2 soft tissue components. At the donor site (subscapular region), only a mild morbidity was observed (DASH score: 21.74 ± 7.3 points). When comparing the patients’ postoperative quality of life to the established values of the healthy German norm population, the observed SF-36 values were within the upper third (>66%) of these established norm values in almost all quality-of-life subcategories. The mild donor site morbidity and the observed quality of life indicate only a small postoperative impairment when using the TDAP-Scap-aa free flap for the reconstruction of extensive maxillofacial defects.
Association between Immediate Postoperative Radiographic Findings and Failed Internal Fixation for Trochanteric Fractures: Systematic Review and Meta-Analysis
Authors: Yamamoto Norio , Tsujimoto Yasushi , Yokoo Suguru , Demiya Koji , Inoue Madoka , Noda Tomoyuki , Ozaki Toshifumi , Yorifuji Takashi
Published: August 2022

Failed internal fixations for trochanteric fractures have a strong negative impact owing to increased postoperative mortality and high medical costs. However, evidence on the prognostic value of postoperative radiographic findings for failed internal fixations is limited. We aimed to clarify the association between comprehensive immediate postoperative radiographic findings and failed internal fixation using relative and absolute risk measures. We followed the meta-analysis of observational studies in epidemiology guidelines and the Cochrane handbook. We searched specific databases in November 2021. The outcomes of interest were failed internal fixation and cut-out. We pooled the odds ratios and 95% confidence intervals using a random-effects model and calculated the number needed to harm for each outcome. Thirty-six studies involving 8938 patients were included. The certainty of evidence in the association between postoperative radiographic findings and failed internal fixation or cut-out was mainly low or very low except for the association between intramedullary malreduction on the anteromedial cortex and failed internal fixation. Moderate certainty of evidence supported that intramedullary malreduction on the anteromedial cortex was associated with failed internal fixation. Most postoperative radiographic findings on immediate postoperative radiographs for trochanteric fractures were uncertain as prognostic factors for failed internal fixations.
Chronic Bronchitis Affects Outcomes in Smokers without Chronic Obstructive Pulmonary Disease (COPD)
Authors: Casara Alvise , Turato Graziella , Marin-Oto Marta , Semenzato Umberto , Biondini Davide , Tinè Mariaenrica , Bernardinello Nicol , Cocconcelli Elisabetta , Cubero Pablo , Balestro Elisabetta , Spagnolo Paolo , Marin Josè M. , Cosio Manuel G. , Saetta Marina , Bazzan Erica
Published: August 2022

Background. Chronic bronchitis (CB) importantly affects outcomes in smokers with COPD, but the effects on smokers without COPD are less well known and less emphasized. The aim of our study was to investigate the possible effects of CB on clinical outcomes in smokers without COPD (noCOPD) and compare them with the effects in smokers with COPD (COPD). Methods. For that purpose, we studied 511 smokers, 302 with and 209 without COPD, followed for 10 years in an academic COPD ambulatory setting. Chronic bronchitis was defined as the presence of cough and sputum production for at least 3 months in each of two consecutive years. All subjects underwent clinical and functional examination with spirometry, diffusion capacity (DLco), 6-min walking test (6MWT), mMRC Dyspnoea Scale, COPD Assessment Test (CAT), and recording of annual frequency of exacerbations. All-cause mortality during follow-up was recorded. Results. 27% of noCOPD and 45% of COPD had CB. noCOPD with CB had lower FEV1 and DLco, worse 6MWT, more dyspnoea, a higher number of exacerbations and lower survival than noCOPD without CB. CB did not affect FEV1 decline in noCOPD but it significantly did in COPD. Conclusions. The presence of chronic bronchitis in smokers without COPD will significantly affect symptoms, quality of life, and survival, underlining the importance of recognizing the condition and managing it accordingly.
Antiplatelet Therapy during the First Year after Acute Coronary Syndrome in a Contemporary Italian Community of over 5 Million Subjects
Authors: Calabria Silvia , Andreotti Felicita , Ronconi Giulia , Dondi Letizia , Campeggi Alice , Piccinni Carlo , Pedrini Antonella , Esposito Immacolata , Addesi Alice , Martini Nello , Maggioni Aldo Pietro
Published: August 2022

Background: Patterns of real-world antiplatelet therapy (APT) are reported to differ from guideline recommendations. This study describes patterns of APT during the year following a hospital diagnosis of acute coronary syndrome (ACS) and possible implications in terms of revascularization rates, rehospitalizations, and costs for the Italian National Health Service. Methods: From >5 million people, patients discharged (=index date) with primary/secondary ACS diagnosis in 2017 were identified by cross-linkage of administrative health data collected by the Ricerca e Salute (ReS) Foundation. Patients were characterized by revascularization rates at index date, APT at one month and one year (with appropriate coverage defined as ≥80% of defined daily doses), and rehospitalizations and healthcare costs during follow-up. Results: From the 2017 ReS database, 7966 (1.46 × 1000 inhabitants) were discharged alive with an ACS diagnosis. Most were >69 years and male. Of these, 83% (6640/7966) received ≥1 recommended antiplatelet agent within one month (treated group): 23% (1870/7966) as single and 60% (4770/7966) as dual APT. Among the 53% undergoing revascularization, 81% received dual APT at one month. Of the 78% with the same APT at one year, 66% showed appropriate coverage. For subjects treated and untreated with APT at one month, one-year rehospitalization rates were 54% and 66%, respectively, and mean per capita costs were EUR 14,316 and EUR 16,552, respectively (hospitalization driving >80% of costs). Conclusions: Among survivors of a hospitalized ACS diagnosis, this analysis shows relatively high APT under-treatment at one month and one year, associated with fewer index revascularization rates, more rehospitalizations, and greater costs. Further initiatives to understand undertreatment and poor adherence should lead to improved health management and savings.
COVID-19-Related ARDS: Key Mechanistic Features and Treatments
Authors: Selickman John , Vrettou Charikleia S. , Mentzelopoulos Spyros D. , Marini John J.
Published: August 2022

Acute respiratory distress syndrome (ARDS) is a heterogeneous syndrome historically characterized by the presence of severe hypoxemia, high-permeability pulmonary edema manifesting as diffuse alveolar infiltrate on chest radiograph, and reduced compliance of the integrated respiratory system as a result of widespread compressive atelectasis and fluid-filled alveoli. Coronavirus disease 19 (COVID-19)-associated ARDS (C-ARDS) is a novel etiology caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that may present with distinct clinical features as a result of the viral pathobiology unique to SARS-CoV-2. In particular, severe injury to the pulmonary vascular endothelium, accompanied by the presence of diffuse microthrombi in the pulmonary microcirculation, can lead to a clinical presentation in which the severity of impaired gas exchange becomes uncoupled from lung capacity and respiratory mechanics. The purpose of this review is to highlight the key mechanistic features of C-ARDS and to discuss the implications these features have on its treatment. In some patients with C-ARDS, rigid adherence to guidelines derived from clinical trials in the pre-COVID era may not be appropriate.
What Are the Biomechanical Properties of an Aortic Aneurysm Associated with Quadricuspid Aortic Valve?
Authors: Lin Siyu , Morgant Marie-Catherine , Marín-Castrillón Diana M. , Bernard Chloé , Boucher Arnaud , Presles Benoît , Lalande Alain , Bouchot Olivier
Published: August 2022

Association of quadricuspid aortic valve (QAV) with ascending aortic aneurysms (AsAA) is rare. A 63-year-old female with hypertension was found (on MRI) to have an ascending aortic aneurysm (52 mm in maximum diameter) and dilatation at the level of the sinotubular junction (38 mm in diameter) associated with quadricuspid aortic valve. An ascending aortic wall replacement surgery was performed. In this study, we focus on the behavior of the aorta associated with QAV considering the in vitro biomechanical characteristics and histology. The properties of QAV are closer to bicuspid aortic valve than tricuspid aortic valve, but with higher wall thickness.
Platelet-to-Lymphocyte Ratio (PLR) Is Not a Predicting Marker of Severity but of Mortality in COVID-19 Patients Admitted to the Emergency Department: A Retrospective Multicenter Study
Authors: Simon Paul , Le Borgne Pierrick , Lefevbre François , Cipolat Lauriane , Remillon Aline , Dib Camille , Hoffmann Mathieu , Gardeur Idalie , Sabah Jonathan , Kepka Sabrina , Bilbault Pascal , Lavoignet Charles-Eric , Abensur Vuillaume Laure
Published: August 2022

(1) Introduction: In the present study, we investigate the prognostic value of platelet-to-lymphocyte ratio (PLR) as a marker of severity and mortality in COVID-19 infection. (2) Methods: Between 1 March and 30 April 2020, we conducted a multicenter, retrospective cohort study of patients with moderate to severe coronavirus 19 (COVID-19), all of whom were hospitalized after being admitted to the emergency department (ED). (3) Results: A total of 1035 patients were included in our study. Neither lymphocytes, platelets or PLR were associated with disease severity. Lymphocyte count was significantly lower and PLR values were significantly higher in the group of patients who died, and both were associated with mortality in the univariate analysis (OR: 0.524, 95% CI: (0.336–0.815), p = 0.004) and (OR: 1.001, 95% CI: (1.000–1.001), p = 0.042), respectively. However, the only biological parameter significantly associated with mortality in the multivariate analysis was platelet count (OR: 0.996, 95% CI: (0.996–1.000), p = 0.027). The best PLR value for predicting mortality in COVID-19 was 356.6 (OR: 3.793, 95% CI: (1.946–7.394), p < 0.001). (4) Conclusion: A high PLR value is however associated with excess mortality.
Normal References of Peak Oxygen Uptake for Cardiorespiratory Fitness Measured with Cardiopulmonary Exercise Testing in Chinese Adults
Authors: Wang Yan , Li Huijuan , Wang Juan , Zhao Wei , Zeng Zhipeng , Hao Li , Yuan Yifang , Lin Yuwei , Wu Yangfeng , Wang Zhengzhen
Published: August 2022

Introduction: This study aims to establish normal reference values of peak oxygen uptake (VO2peak) for cardiorespiratory fitness (CRF) in Chinese adults using cardiorespiratory exercise testing (CPET). Methods: A cross-sectional study was done in four communities, two in the North (Beijing) and two in the South (Hezhou, Guangxi) of China from 1 January 2017 to 31 December 2018, with one urban and one rural in each region. Out of 1642 participants screened, 1114 were eligible and completed CPET using a cycle ergometer (Ergosana320F) without abnormal ECG and were included in the analysis. The 2nd and 98th percentiles of V·O2peak were used as the lower and upper limits of the normal reference values. Results: Significant difference in mean V·O2peak was shown between men (27.0 mL·min−1·kg−1) and women (23.7 mL·min−1·kg−1). The mean V·O2peak decreased with age in both sexes, from 35.8 mL·min−1·kg−1 in age 20–29 years to 20.5 mL·min−1·kg−1 in 70–79 years in men and from 29.2 mL·min−1·kg−1 to 17.0 mL·min−1·kg−1 in women. Thus, the age- and sex-specific normal reference values of V·O2peak were presented for each 10-year age group by men and women separately. Conclusions: This first community-based study in China provides age- and sex-specific normal references of V·O2peak as a measure of CRF in Chinese adults, which differed significantly from those established in Western populations. Future studies with national representative samples should be warranted.
Uterine Factor Infertility, a Systematic Review
Authors: Sallée Camille , Margueritte François , Marquet Pierre , Piver Pascal , Aubard Yves , Lavoué Vincent , Dion Ludivine , Gauthier Tristan
Published: August 2022

Uterine factor infertility (UFI) is defined as a condition resulting from either a complete lack of a uterus or a non-functioning uterus due to many causes. The exact prevalence of UFI is currently unknown, while treatments to achieve pregnancy are very limited. To evaluate the prevalence of this condition within its different causes, we carried out a worldwide systematic review on UFI. We performed research on the prevalence of UFI and its various causes throughout the world, according to the PRISMA criteria. A total of 188 studies were included in qualitative synthesis. UFI accounted for 2.1 to 16.7% of the causes of female infertility. We tried to evaluate the proportion of the different causes of UFI: uterine agenesia, hysterectomies, uterine malformations, uterine irradiation, adenomyosis, synechiae and Asherman syndrome, uterine myomas and uterine polyps. However, the data available in countries and studies were highly heterogenous. This present systematic review underlines the lack of a consensual definition of UFI. A national register of patients with UFI based on a consensual definition of Absolute Uterine Factor Infertility and Non-Absolute Uterine Factor Infertility would be helpful for women, whose desire for pregnancy has reached a dead end.
The Management of Portal Vein Thrombosis after Adult Liver Transplantation: A Case Series and Review of the Literature
Authors: Hu Liang-Shuo , Zhao Zhen , Li Tao , Li Qin-Shan , Lu Yi , Wang Bo
Published: August 2022

Background: Portal vein thrombosis (PVT) after adult liver transplantation (LT) is a rare but serious complication with no consensus on the ideal treatment. We report a case series and a comprehensive review of the literature on PVT after LT to discuss the therapeutic options. Methods: The clinical data of 360 adult patients (≥18 years of age) who underwent LT from January 2017 to January 2020 were reviewed, and a comprehensive search of PubMed and Web of Science was conducted. Patients diagnosed with PVT after LT were identified, and relevant risk factors and therapies were analyzed. Results: Among the 360 patients, 7 (1.94%) developed PVT after LT. Onset of PVT within one week after LT was found in six patients (85.71%). Four of the seven patients with PVT received systemic anticoagulation (low molecular weight heparin and warfarin) therapy. Minimally invasive interventional therapies combined with systemic anticoagulation (heparin and warfarin) were applied for three patients, two of whom died because of severe abdominal hemorrhage and liver failure. Of the 33 cases reported in the literature, minimally invasive interventional therapy combined with systematic anticoagulation or sclerotherapy were the most-used methods (20/33). Systemic anticoagulation was administered to four patients, and surgical operation (thrombectomy; portosystemic shunt and retransplantation) was performed for nine patients. Among these 33 patients, 4 eventually died. Conclusions: Interventional therapy combined with systemic anticoagulation is a good choice for the management of PVT after LT, and in our experience, systemic anticoagulation alone can also have a positive effect for early PVT patients.
The Effect of Roux-en-Y Gastric Bypass on Non-Alcoholic Fatty Liver Disease Fibrosis Assessed by FIB-4 and NFS Scores—An 11.6-Year Follow-Up Study
Authors: Sandvik Elfrid Christine Smith , Aasarød Kristin Matre , Johnsen Gjermund , Hoff Dag Arne Lihaug , Kulseng Bård , Hyldmo Åsne Ask , Græslie Hallvard , Nymo Siren , Sandvik Jorunn , Fossmark Reidar
Published: August 2022

Severe obesity is a strong risk factor for non-alcoholic fatty liver disease (NAFLD). Roux-en-Y gastric bypass (RYGB) surgery effectively induces weight loss, but few studies have described the long-term effects of RYGB on NAFLD-related fibrosis. Data from 220 patients with severe obesity operated by RYGB in Central Norway were analysed. Variables incorporated in NAFLD Fibrosis Score (NFS), Fibrosis-4 (FIB-4) index and anthropometric data were collected before surgery and a mean of 11.6 years postoperatively. FIB-4 > 1.3 or NFS > 0.675 were used as cut-off values for advanced fibrosis. Proportions with advanced fibrosis decreased from 24% to 14% assessed by FIB-4 and from 8.6% to 2.3% using NFS, with resolution rates of advanced fibrosis of 42% and 73%, respectively. The shift towards lower fibrosis categories was significant (NFS p < 0.0001; FIB-4 p = 0.002). NFS decreased from −1.32 (IQR −2.33–−0.39) to −1.71 (IQR −2.49–−0.95, p < 0.001) 11.6 years after surgery, whereas FIB-4 did not change: 0.81 (IQR 0.59–1.25) to 0.89 (IQR 0.69–1.16, p = 0.556). There were weak correlations between change in fibrosis scores and weight loss. In conclusion, the majority of patients with advanced fibrosis at baseline had improvement after 11.6 years. Factors associated with reduction in fibrosis were not identified.
Recent Increases in Influenza-Related Hospitalizations, Critical Care Resource Use, and In-Hospital Mortality: A 10-Year Population-Based Study in South Korea
Authors: Hong Tae Hwa , Lee Hyung Seok , Kim Nam-Eun , Lee Kyu Jin , Kim Yong Kyun , An Jung Nam , Kim Joo-Hee , Kim Hyung Won , Park Sunghoon
Published: August 2022

Background: Long-term trends in influenza-related hospitalizations, critical care resource use, and hospital outcomes since the 2009 H1N1 influenza pandemic season have been rarely studied for adult populations. Materials and Methods: Adult patients from the Korean Health Insurance Review and Assessment Service who were hospitalized with influenza over a 10-year period (2009–2019) were analyzed. The incidence rates of hospitalization, critical care resource use, and in-hospital death were calculated using mid-year population census data. Results: In total, 300,152 hospitalized patients with influenza were identified (men, 35.7%; admission to tertiary hospitals, 9.4%). Although the age-adjusted hospitalization rate initially decreased since the 2009 H1N1 pandemic (52.61/100,000 population in 2009/2010), it began to increase again in 2013/2014 and reached a peak of 169.86/100,000 population in 2017/2018 (p < 0.001). The in-hospital mortality rate showed a similar increasing trend as the hospitalization, with a peak of 1.44/100,000 population in 2017/2018 (vs. 0.35/100,000 population in 2009/2010; p < 0.001). The high incidence rates of both hospitalization and in-hospital mortality were mainly attributable to patients aged ≥60 years. The rate of intensive care unit admission and the use of mechanical ventilation, continuous renal replacement therapy and vasopressors have also increased from the 2013/2014 season. The incidence of heart failure was the most frequent complication investigated, with a three-fold increase in the last two seasons since 2009/2010. In multivariate analysis adjusted for covariates, among hospitalized patients, type of hospitals and 2009 H1N1 pandemic season were associated with in-hospital mortality. Conclusions: We confirmed that the rates of hospitalization, critical care resource use, and in-hospital mortality by influenza have increased again in recent years. Therefore, strategies are needed to reduce infections and optimize resource use with a greater focus on older people.
Dermoscopy Use Leads to Earlier Cutaneous Melanoma Diagnosis in Terms of Invasiveness and Size? A Single-Center, Retrospective Experience
Authors: Nazzaro Gianluca , Passoni Emanuela , Pozzessere Fabio , Maronese Carlo Alberto , Marzano Angelo Valerio
Published: August 2022

Background: The incidence of cutaneous melanoma has risen in recent years. The aim of this study was to compare cutaneous melanomas diagnosed at the Dermatology Unit of Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy, from 2006 to 2020 and between two specific biennia, i.e., 2006–2007 and 2019–2020. Methods: Retrospective chart review, with dermoscopic image collection, of cutaneous melanomas diagnosed at the Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy, from 1 January 2006 to 31 December 2020 Results: A statistically significant increase was shown in the proportions of in situ melanoma and melanoma measuring less than 6 mm, i.e., small-diameter melanoma (SDM), across the studied period (p < 0.001). Moreover, in the biennium 2006–2007, among 220 melanoma diagnoses, 6 were in situ (2.7%), as compared with 68 melanomas in situ out of a total of 236 (28.8%) melanomas diagnosed in the biennium 2019–2020. A statistically significant difference in the proportion of in situ melanoma between the two biennia was demonstrated (p < 0.001). Furthermore, during the first biennium, 27/220 (12.3%) SDM were identified, as compared with 61/236 (25.9%) in the last. A statistically significant difference was shown in the proportion of SDM between the two (p < 0.001). Conclusions: The percentage of in situ melanomas and those that can be detected at a diameter <6 mm has increased. The latter has been shown to be around one-third of excised lesions, thus undermining the practicality of the ABCD mnemonic. Dermoscopic criteria for SDM are needed to help further refine melanoma diagnosis.
Primary Epstein–Barr Virus-Positive Mucocutaneous Ulcer of Esophagus: A Rare Case Report
Authors: Sun Chunping , Wang Qingya , Dong Yujun , Nong Lin , Cai Yunlong , Wang Lihong , Sun Yuhua , Wang Wensheng , Liu Xinmin
Published: August 2022

Primary EBV-positive mucocutaneous ulcer (EBVMCU) is a rare and indolent disorder occurring in the oropharynx, skin, and gastrointestinal tract, with remission after removal of the immunosuppressive causes. We present a 69-year-old woman with heartburn, regurgitation of gastric acid, enlarged lymph nodes, and parotid glands. The endoscopic examination showed a circumscribed ulcer in the lower esophagus. A biopsy pathology indicated an esophageal EBV-associated lymphoproliferative disorder and a parotid gland/lymph node indolent B-cell lymphoma. Interestingly, the patient did not undergo any treatment, but the endoscopic ulcer improved significantly after more than 2 months. The last pathology showed EBV negativity, and EBVMCU was considered in combination with clinical and endoscopic manifestations. We followed up with the patient at 6 months, and the symptoms of acid reflux and heartburn had disappeared. Our case demonstrates that EBVMCU may occur in the esophagus with spontaneous regression.
The Role of TSHR, PTEN and RASSF1A Promoters’ Methylation Status for Non-Invasive Detection of Papillary Thyroid Carcinoma
Authors: Klimaitė Raimonda , Kazokaitė Mintautė , Kondrotienė Aistė , Daukšienė Dalia , Sabaliauskaitė Rasa , Žukauskaitė Kristina , Žilaitienė Birutė , Jarmalaitė Sonata , Daukša Albertas
Published: August 2022

Aim: We investigated whether a difference exists between TSHR, PTEN and RASSF1A methylation status in plasma of subjects with papillary thyroid cancer (PTC). Methods: Peripheral blood samples were collected from 68 patients with PTC and 86 healthy controls (HC). Thyroid cancer tissue and corresponding adjacent normal tissue methylation levels were analyzed. DNA methylation level changes in TSHR, PTEN and RASSF1A genes were analyzed by quantitative methylation-sensitive polymerase chain reaction. Results: We observed that the methylation level of TSHR was significantly higher in the thyroid cancer tissue compared to adjacent normal tissue (p = 0.040). TSHR methylation levels in the PTC group plasma samples were significantly higher compared to HC (p = 0.022). After surgery, PTC plasma samples showed lower TSHR and PTEN methylation levels compared to the levels before surgery (p = 0.003, p = 0.031, respectively). The TSHR methylation level was significantly higher in PTC with larger tumor size (>2 cm) (p < 0.001), and lymph node metastases (p = 0.01), lymphovascular invasion (p = 0.02) and multifocality (p = 0.013) 0ROC analysis revealed that the TSHR methylation level provides high accuracy in distinguishing PTC from HC (p = 0.022, AUC of 0.616). Conclusion: TSHR methylation in peripheral blood samples is expected to be a sensitive and specific minimally invasive tool for the diagnosis of PTC, especially in combination with other diagnostic means.
Artificial Intelligence-Assisted Renal Pathology: Advances and Prospects
Authors: Wang Yiqin , Wen Qiong , Jin Luhua , Chen Wei
Published: August 2022

Digital imaging and advanced microscopy play a pivotal role in the diagnosis of kidney diseases. In recent years, great achievements have been made in digital imaging, providing novel approaches for precise quantitative assessments of nephropathology and relieving burdens of renal pathologists. Developing novel methods of artificial intelligence (AI)-assisted technology through multidisciplinary interaction among computer engineers, renal specialists, and nephropathologists could prove beneficial for renal pathology diagnoses. An increasing number of publications has demonstrated the rapid growth of AI-based technology in nephrology. In this review, we offer an overview of AI-assisted renal pathology, including AI concepts and the workflow of processing digital image data, focusing on the impressive advances of AI application in disease-specific backgrounds. In particular, this review describes the applied computer vision algorithms for the segmentation of kidney structures, diagnosis of specific pathological changes, and prognosis prediction based on images. Lastly, we discuss challenges and prospects to provide an objective view of this topic.