bluuebunny/crossref_metadata_2025_split huggingface dataset:
How obesity affects the benefits of holmium laser enucleation of the prostate for the treatment of male lower urinary tract symptoms
Authors: Tamalunas Alexander , Westhofen Thilo , Schott Melanie , Keller Patrick , Atzler Michael , Stief Christian G , Magistro Giuseppe 
Published: September 2021

Objectives: Holmium laser enucleation of the prostate (HoLEP) can be used regardless of prostate size and offers durable long-term results for patients suffering from lower urinary tract symptoms (LUTS)/benign prostatic obstruction (BPO), with reduced perioperative morbidity. In most western societies almost half of the population are overweight, and obesity itself is often a risk factor for surgical treatment of patients. We therefore analysed the impact of body mass index (BMI) on outcomes and perioperative morbidity in patients undergoing HoLEP for LUTS at our tertiary referral centre. Methods: We retrospectively collected data for 877 patients who underwent HoLEP for LUTS/BPO between 2014 and 2018 and divided patients into group 1 (BMI<25), 2 (BMI 25<30), and 3 (BMI⩾30). We analysed perioperative parameters, safety, and short-term functional outcomes. Results: In preoperative patient characteristics we observed a similar LUTS profile throughout our patient cohorts. The highest proportion of ASA score ⩾III was observed in the obese patient cohort. Enucleation time was significantly prolonged in morbidly obese patients and operative speed was significantly slower, without difference in perioperative complications. Functional outcomes were assessed 30 days post-surgery with significant improvement in IPSS, quality of life (QoL) and Qmax for all groups. Conclusion: Although operating on overweight and obese patients takes significantly longer, HoLEP is efficient and offers acceptable perioperative complication rates even in morbidly obese patients (BMI⩾30). Level of evidence: Not applicable.
Economic Analysis of Specialist Referral Patterns in Mackay, Queensland Following HealthPathways Implementation
Authors: Blythe Robin , Lee Xing , Simmons Toni , Cox Janine , McLean Kathleen , Barfield Josephine , Kularatna Sanjeewa 
Published: September 2021

Introduction: HealthPathways is a clinical information portal developed in New Zealand that enables general practitioners to manage and refer their patients in a local context. We analyzed specialist outpatient appointment costs in Mackay, Queensland before and after HealthPathways implementation. Methods: We retrospectively examined specialist outpatient costs for patients referred by Mackay general practitioners for conditions with varying levels of HealthPathways implementation. Ranked from most clinical pathways available to none, chronic diabetes, cardiology, respiratory, and urology visits from January to March 2015, pre-pathways, and January to March 2017, post-pathways, were assessed. Monte Carlo simulation was used to estimate cost changes. Per-visit costs were multiplied by visit numbers to estimate policy impact. Results: The mean cost per visit increased from $220 to $305 for diabetes and $270 to $323 for respiratory, and decreased from $296 to $257 for cardiology and $444 to $293 for urology. The policy impact for each disease group over 3 months after accounting for visit numbers was a likely saving of $30 360 for diabetes and $10 270 for cardiology, and a likely cost increase of $24 449 for respiratory and $20 536 for urology. Conclusions: We observed that conditions with more comprehensive clinical pathways cost Mackay HHS substantially less following implementation. Costs for low and no pathway implementation referrals increased slightly over the same period.
How I treat neurologic complications in patients with lymphoid cancer
Authors: Nayak Lakshmi , Batchelor Tracy T. 
Published: September 2021

Abstract
Neurologic complications of lymphoid cancer can be challenging to recognize and treat. The nervous system can be affected directly by hematogenous or local spread of lymphoma. Indirect neurologic effects of lymphoma include paraneoplastic syndromes and vascular complications. Lymphoma treatments can also cause neurologic complications. Early identification and treatment are crucial to stabilize or reverse neurologic deficits, prevent further nervous system injury, and optimize overall oncologic therapy. This article provides an overview of the different neurologic complications of lymphoma and its treatments, in addition to presenting case studies that emphasize commonly encountered clinical scenarios.
Current evidence on the efficacy and safety of generic imatinib in CML and the impact of generics on health care costs
Authors: Erçalışkan Abdülkadir , Seyhan Erdoğan Duygu , Eşkazan Ahmet Emre 
Published: September 2021

Abstract
Since the introduction of imatinib, the management of chronic myeloid leukemia (CML) has changed considerably. Tyrosine kinase inhibitors (TKIs) are the mainstay of CML treatment; however, the high financial burden of TKIs can be problematic for both the patients and health care systems. After the emergence of generics, reimbursement policies of many countries have changed, and generics offered an alternative treatment option for CML patients. There are many papers published on the use of generics in CML patients with conflicting results regarding both efficacy and safety. In this paper, we systematically reviewed the current literature on generic imatinib use in CML, and 36 papers were evaluated. Both in vitro and in vivo studies of generic imatinib showed comparable results with branded imatinib in terms of bioequivalence and bioavailability. In most studies, generics were comparable with the original molecule in terms of efficacy and safety, both in newly diagnosed patients and after switching from Gleevec. Some generic studies showed contradictory findings regarding efficacy and toxicity, and these differences can be attributed to some factors including the use of different generics in different countries. Both in hypothetical models and in real life, introduction of generic imatinib caused significant reduction in health care costs. In conclusion, generics are not inferior to original imatinib in terms of efficacy with an acceptable toxicity profile. Notwithstanding the generally favorable efficacy and safety of generics worldwide to date, we most probably still need more time to draw firmer conclusions on the longer-term outcomes of generics.
Long-term efficacy and safety of CT-P10 or rituximab in untreated advanced follicular lymphoma: a randomized phase 3 study
Authors: Buske Christian , Jurczak Wojciech , Sancho Juan-Manuel , Zhavrid Edvard , Kim Jin Seok , Hernández-Rivas José-Ángel , Prokharau Aliaksandr , Vasilica Mariana , Nagarkar Rajnish , Kwak Larry , Kim Won-Seog , Lee SangJoon , Kim SungHyun , Ahn KeumYoung , Ogura Michinori 
Published: September 2021

Abstract
Rituximab biosimilars are a cornerstone of treatment of advanced-stage follicular lymphoma (FL). This double-blind, parallel-group, phase 3 trial randomized (1:1) adults (≥18 years) with stage III to IV indolent B-cell lymphoma, including grades 1 to 3a FL, to receive CT-P10 or rituximab (375 mg/m2 IV), with cyclophosphamide, vincristine, and prednisone, every 3 weeks for 8 cycles (induction period). Patients achieving complete response (CR), unconfirmed CR, or partial response (PR) received CT-P10 or rituximab maintenance for 2 years (375 mg/m2, every 8 weeks). Primary end points were previously reported, proving noninferiority of efficacy and pharmacokinetic equivalence of CT-P10 to rituximab. Secondary end points included overall response rate (PR+CR) during the induction period per 2007 International Working Group (IWG) criteria, survival analyses, and overall safety. Between 28 July 2014 and 29 December 2015, 140 patients were randomized (70 per group). Median follow-up was 39.9 months (interquartile range, 36.7-43.5). Per 1999 IWG criteria, 4-year Kaplan-Meier estimates (95% confidence interval [CI]) for CT-P10 and rituximab were 61% (47% to 73%) and 55% (36% to 70%) for progression-free survival (hazard ratio, 1.33 [95% CI, 0.67-2.63]; P=.409), respectively, and 88% (77% to 94%) and 93% (83% to 97%) for overall survival (5.29 [0.84-33.53]; P=.077). Overall, 90% (CT-P10) and 86% (rituximab) of patients experienced treatment-emergent adverse events. Long-term safety profiles were similar between groups. Findings confirm favorable outcomes for CT-P10–treated patients with advanced-stage FL and demonstrate comparable long-term efficacy and overall safety between CT-P10 and rituximab. This trial was registered at www.clinicaltrials.gov as #NCT02162771.
Storage temperature determines platelet GPVI levels and function in mice and humans
Authors: Miles Jeffrey , Bailey S. Lawrence , Obenaus Ava M. , Mollica Molly Y. , Usaneerungrueng Chomkan , Byrne Daire , Fang Lydia , Flynn Jake R. , Corson Jill , Osborne Barbara , Houck Katie , Wang Yi , Shen Yu , Fu Xiaoyun , Dong Jing-Fei , Sniadecki Nathan J. , Stolla Moritz 
Published: September 2021

Abstract
Platelets are currently stored at room temperature before transfusion to maximize circulation time. This approach has numerous downsides, including limited storage duration, bacterial growth risk, and increased costs. Cold storage could alleviate these problems. However, the functional consequences of cold exposure for platelets are poorly understood. In the present study, we compared the function of cold-stored platelets (CSP) with that of room temperature–stored platelets (RSP) in vitro, in vivo, and posttransfusion. CSP formed larger aggregates under in vitro shear while generating similar contractile forces compared with RSP. We found significantly reduced glycoprotein VI (GPVI) levels after cold exposure of 5 to 7 days. After transfusion into humans, CSP were mostly equivalent to RSP; however, their rate of aggregation in response to the GPVI agonist collagen was significantly lower. In a mouse model of platelet transfusion, we found a significantly lower response rate to the GPVI-dependent agonist convulxin and significantly lower GPVI levels on the surface of transfused platelets after cold storage. In summary, our data support an immediate but short-lived benefit of cold storage and highlight the need for thorough investigations of CSP. This trial was registered at www.clinicaltrials.gov as #NCT03787927.
Fungal keratitis after small incision lenticule extraction (SMILE): a case report and review of the literature
Authors: Soleimani Mohammad , Haydar Ali A. 
Published: September 2021

Abstract
Purpose
To report a case of perforated fungal keratitis after small incision lenticule extraction (SMILE) treated with penetrating keratoplasty (PKP).

Methods
Case report and literature review.

Results
A 41-year-old woman presented with culture-proven unilateral fungal keratitis 4 days after uneventful SMILE. Her visual acuity was hand motion. The patient was treated with voriconazole irrigation (50 μm/0.1 ml) of the pocket and intrastromal voriconazole injection, in addition to systemic and topical antifungals. Despite aggressive management and decreased infiltration, the cornea was perforated and subsequently treated with PKP.

Conclusions
Infectious keratitis after SMILE is unusual. To our knowledge, this is the first report of perforated fungal keratitis post-SMILE. PKP eradicated the infection.
miR-153/KCNQ4 axis contributes to noise-induced hearing loss in a mouse model
Authors: Wang Qin , Li Wei , Cai Cuiyun , Hu Peng , Lai Ruosha 
Published: September 2021

AbstractDamage to the cochlear sensory epithelium is a key contributor to noise-induced sensorineural hearing loss (SNHL). KCNQ4 plays an important role in the cochlear potassium circulation and outer hair cells survival. As miR-153 can target and regulate KCNQ4, we sought to study the role of miR-153 in SNHL. 12-week-old male CBA/J mice were exposed to 2–20 kHz broadband noise at 96 dB SPL to induce temporary threshold shifts and 101 dB SPL to induce permanent threshold shifts. Hearing loss was determined by auditory brainstem responses (ABR). Relative expression of miR-153 and KCNQ4 in mice cochlea were determined by Real-Time quantitative PCR. miR-153 mimics were co-transfected with wild type or mutated KCNQ4 into HEK293 cells. Luciferase reporter assay was used to validate the binding between miR-153 and KCNQ4. AAV-sp-153 was constructed and administrated intra-peritoneally 24- and 2-h prior and immediately after noise exposure to knockdown miR-153. The KCNQ4 is mainly expressed in outer hair cells (OHCs). We showed that the expression of KCNQ4 in mice cochlea was reduced and miR-153 expression was significantly increased after noise exposure compared to control. miR-153 bound to 3′UTR of KNCQ4, and the knockdown of miR-153 with the AAV-sp-153 administration restored KCNQ4 mRNA and protein expression. In addition, the knockdown of miR-153 reduced ABR threshold shifts at 8, 16, and 32 kHz after permanent threshold shifts (PTS) noise exposure. Correspondingly, OHC losses were attenuated with inhibition of miR-153. This study demonstrates that miR-153 inhibition significantly restores KNCQ4 in cochlea after noise exposure, which attenuates SNHL. Our study provides a new potential therapeutic target in the prevention and treatment of SNHL.
Sevoflurane blocks glioma malignant development by upregulating circRELN through circRELN-mediated miR-1290/RORA axis
Authors: Kang Xiaofang , Li Hongxia , Zhang Zaiwang 
Published: September 2021

Abstract
Background
Sevoflurane (Sev) has been reported to inhibit cancer development, and sevoflurane treatment in cancers is implicated with the deregulation of specific non-coding RNAs (ncRNAs). This study aimed to investigate the relationship between sevoflurane and circular RNA reelin (circRELN) in glioma.

Methods
The expression of circRELN, microRNA-1290 (miR-1290) and RAR-related orphan receptor A (RORA) was measured by quantitative real-time PCR (qPCR). Cell proliferative capacity was assessed by cell counting kit-8 (CCK-8) and colony formation assays. Cell apoptosis and cell cycle distribution were monitored by flow cytometry assay. Cell migration was assessed by wound healing assay and transwell assay, and cell invasion was assessed by transwell assay. The protein levels of matrix metalloproteinase-2 (MMP2), MMP9 and RORA were quantified by western blot. Tumor growth in vivo was assessed by Xenograft models. The binding relationship between miR-1290 and circRELN or RORA was verified by dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay.

Results
We found that circRELN expression was declined in glioma tissues and cells, while Sev treatment enhanced circRELN expression. In function, Sev notably inhibited glioma cell proliferation, migration and invasion and promoted apoptosis and cell cycle arrest, while circRELN knockdown reversed these effects. MiR-1290 served as a target of circRELN, and glioma cell malignant phenotypes recovered by circRELN knockdown were partly repressed by miR-1290 deficiency. In addition, RORA was a target of miR-1290, and glioma cell malignant phenotypes promoted by miR-1290 restoration were partly blocked by RORA overexpression. CircRELN regulated RORA expression by targeting miR-1290. In Xenograft models, Sev inhibited tumor growth by upregulating circRELN.

Conclusion
Sev blocked the progression of glioma by increasing circRELN expression, and circRELN played roles in glioma partly by regulating the miR-1290/RORA network.
Clinical characteristics of children with airway malacia complicated by pneumonia
Authors: Wang Ting , Xu Qiuyan , Dai Ge , Hong Yu , Chen Zhengrong , Lu Min , Yan Yongdong , Jiang Wujun 
Published: September 2021

AbstractBackgroundAirway malacia is an important cause of noisy breathing, recurrent wheezing and respiratory infections, chronic coughing, and episodes of respiratory distress in young children. As the clinical manifestations of airway malacia are not common, many clinicians have insufficient understanding of this disease. So the purpose of this study is to summarize the pathogenic bacteria and clinical manifestations of airway softening complicated with pneumonia in children.MethodsChildren hospitalized with airway malacia complicated by pneumonia were eligible for enrollment from January 1, 2013 to December 31, 2019. Medical records of patients were reviewed for etiology, clinical characteristics, and laboratory examination results.ResultsA total of 164 pneumonia patients with airway malacia were admitted. The male-to-female ratio was 3:1. The age of patients ranged from 1 month to 4 years old. The median age was 6 (3–10) months. The most commonly detected pathogen wereMycoplasma pneumoniae(25/164, 15.24%),Streptococcus pneumoniae(18/164, 10.98%), and respiratory syncytial virus (16/164, 9.76%). Common signs among the 164 patients with confirmed airway malacia included cough (98.78%), wheezing (67.07%), fever (35.37%), intercostal retractions (23.17%), dyspnea (10.98%), cyanosis (11.11%), and crackles (50%). Compared with those without airway malacia, the incidence of premature delivery and mechanical ventilation was higher, and the duration of symptoms before admission (median, 13.5 d) and hospital stay (median 10.0 d) were longer. Of the children with pneumonia, 11.59% of those with airway malacia required supplemental oxygen compared with 4.88% of those without airway malacia (p < 0.05).ConclusionThe median age of children with airway malacia was 6 months. The most common pathogen in patients with airway malacia complicated by pneumonia wasMycoplasma pneumoniae. Patients with airway malacia complicated by pneumonia often presented with a longer disease course, more severe symptoms, and had delayed recovery.
Detection of aerobe–anaerobe mixed infection by metagenomic next-generation sequencing in an adult suffering from descending necrotizing mediastinitis
Authors: Duan Jing , Zhang Chuncheng , Che Xiaoshuang , Fu Juanjuan , Pang Feng , Zhao Qigang , You Zhiqing 
Published: September 2021

Abstract
Background
Descending necrotizing mediastinitis (DNM) is one of the most virulent forms of mediastinitis. The main causes of high mortality in DNM are believed to stem from difficulty and delay in the diagnosis. Fast and accurate identification of pathogens is important for the treatment of these patients. Metagenomics next-generation sequencing (mNGS) is a powerful tool to identify all kinds of pathogens, especially for rare and complex infections.

Case presentation
A 64-year-old male patient was admitted to the intensive care unit (ICU) with unconsciousness, dyspnea, and swelling in the mandible and neck. Computed tomography (CT) scan results combined with clinical laboratory examination indicated DNM. Vancomycin and imipenem were used, and vacuum sealing drainage was applied for debridement and drainage of the infected area. The positive mNGS results of drainage fluid confirmed the presence of mixed infection caused by Streptococcus anginosus, Prevotella oris, and several other anaerobes. The antibiotics were adjusted to piperacillin/tazobactam and tinidazole according to the mNGS results and antimicrobial susceptibility testing of cultured pathogens. After 11 days of antibiotic therapy, the infection symptoms of the neck and mediastinum improved, and the patient was transferred out of the ICU on the 26th day after negative result of drainage fluid culture.

Conclusion
This case suggested that mNGS is a promising technology for precise and fast pathogens identification with high sensitivity, which may guide the diagnosis of infectious diseases in the future trend.
Diagnostic utility of metabolic parameters on FDG PET/CT for lymph node metastasis in patients with cN2 non-small cell lung cancer
Authors: Nakanishi Keita , Nakamura Shota , Sugiyama Tomoshi , Kadomatsu Yuka , Ueno Harushi , Goto Masaki , Ozeki Naoki , Fukui Takayuki , Iwano Shingo , Chen-Yoshikawa Toyofumi Fengshi 
Published: September 2021

Abstract
Background
The aim of this study was to assess the diagnostic utility of metabolic parameters on fluorine-18-fluoro-2-deoxy-D-glucose-positron emission tomography (FDG-PET)/computed tomography (CT) for predicting lymph node (LN) metastasis in patients with cN2 non-small cell lung cancer (NSCLC).

Methods
We retrospectively reviewed patients who underwent surgery for cN2 NSCLC between 2007 and 2020. Those who had clinically diagnosed positive hilar and mediastinal LNs by routine CT and PET/CT imaging were investigated. To measure the metabolic parameters of LNs, the data according to maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), total lesion glycolysis (TLG), and LN-to-primary tumor ratio of SUVmax (LPR) were examined. The diagnosis of each retrieved LN was confirmed based on histopathological examination of surgical tissue specimens. Receiver operating characteristics (ROC) curves with area under the curve (AUC) calculations and multivariate analysis by logistic regression were performed.

Results
Forty-five patients with 84 clinically diagnosed positive hilar or mediastinal LNs were enrolled in the present study. Of the 84 LNs, 63 LNs were pathologically proven as positive (75%). The SUVmax, MTV, TLG, and LPR of LN metastasis were significantly higher than those of benign nodes. In the ROC analysis, the AUC value of LPR [AUC, 0.776; 95% confidence interval (CI), 0.640–0.913] was higher than that of LN SUVmax (AUC, 0.753; 95% CI, 0.626–0.880) or LN TLG3.5 (AUC, 0.746; 95% CI, 0.607–0.885). Using the optimal LPR cutoff value of 0.47, the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 84.1, 66.7, 88.3, 58.3, and 79.8%, respectively. Multivariate analysis by logistic regression showed that LPR was an independent predictor for LN metastasis (odds ratio, 6.45; 95% CI, 1.785–23.301; P = 0.004). In the subgroup analysis of adenocarcinoma patients (n = 18; 32 LNs), TLG3.5 was a better predictor (AUC, 0.816; 95% CI, 0.639–0.985) than LPR (AUC, 0.792; 95% CI, 0.599–0.986) or LN SUVmax (AUC, 0.792; 95% CI, 0.625–0.959).

Conclusions
Our findings suggest that LPR on FDG-PET is a useful predictor for LN metastasis in patients with cN2 NSCLC. TLG can be a good predictor for LN metastasis in patients with adenocarcinoma.