bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Randomized Comparison of Nivolumab versus Nivolumab + Docetaxel for Previously Treated Advanced or Recurrent ICI-Naïve Non–Small Cell Lung Cancer: TORG1630
Authors: Taniguchi Yuri , Shimokawa Tsuneo , Takiguchi Yuichi , Misumi Toshihiro , Nakamura Yukiko , Kawashima Yosuke , Furuya Naoki , Shiraishi Yoshimasa , Harada Toshiyuki , Tanaka Hisashi , Miura Satoru , Uchiyama Ayumi , Nakahara Yoshiro , Tokito Takaaki , Naoki Katsuhiko , Bessho Akihiro , Goto Yasuhiro , Seike Masahiro , Okamoto Hiroaki 
Published: August 2022

Abstract

Purpose:
The addition of cytotoxic chemotherapy to immune-checkpoint inhibitor (ICI) may enhance antitumor effects. We conducted an open-label randomized phase II/III study to evaluate nivolumab + docetaxel combination therapy in comparison with nivolumab monotherapy for previously treated ICI-naïve non–small cell lung cancer (NSCLC).

Patients and Methods:
The primary endpoint of the phase III study was overall survival (OS), and the secondary endpoints included progression-free survival (PFS), overall response rate (ORR), and toxicity. As ICI and platinum-doublet combination chemotherapy was approved in the first-line setting during this study, patient accrual was discontinued.

Results:
One hundred twenty-eight patients (each arm, n = 64) were included in the full analysis set. The median OS in nivolumab (arm A) and nivolumab + docetaxel (arm B) was 14.7 months (95% CI, 11.4–18.7) and 23.1 months (95% CI, 16.7–NR), respectively. The HR for OS was 0.63 (90% CI, 0.42–0.95; P = 0.0310). The median PFS in arms A and arm B was 3.1 months (95% CI, 2.0–3.9) and 6.7 months (95% CI, 3.8–9.4), respectively. The HR for progression was 0.58 (95% CI, 0.39–0.88; P = 0.0095). The ORR was 14.0% (95% CI, 6.3–25.8) in arm A and 41.8% (95% CI, 28.7–55.9) in arm B. Hematotoxicity and gastrointestinal adverse events were more common in arm B than in arm A. Two treatment-related deaths were observed, including one patient in arm A who died of pneumonitis and one in arm B who died of myocarditis.

Conclusions:
Despite a slightly elevated toxicity, the addition of docetaxel to nivolumab has significantly prolonged the OS and PFS of patients with previously treated ICI-naïve NSCLC.
High-Density Lipoprotein and Long-Term Incidence and Progression of Aortic Valve Calcification: The Multi-Ethnic Study of Atherosclerosis
Authors: Bortnick Anna E. , Buzkova Petra , Otvos James D. , Jensen Majken K. , Tsai Michael Y. , Budoff Matthew J. , Mackey Rachel H. , El Khoudary Samar R. , Favari Elda , Kim Ryung S. , Rodriguez Carlos J. , Thanassoulis George , Kizer Jorge R. 
Published: August 2022

Background:
Aortic valve calcification (AVC) shares pathological features with atherosclerosis. Lipoprotein components have been detected in aortic valve tissue, including HDL (high-density lipoprotein). HDL measures have inverse associations with cardiovascular disease, but relationships with long-term AVC progression are unclear. We investigated associations of HDL cholesterol, HDL-particle number and size, apoC3-defined HDL subtypes, and, secondarily, CETP (cholesteryl ester transfer protein) mass and activity, with long-term incidence and progression of AVC.

Methods:
We used linear mixed-effects models to evaluate the associations of baseline HDL indices with AVC. AVC was quantified by Agatston scoring of up to 3 serial computed tomography scans over a median of 8.9 (maximum 11.2) years of follow-up in the Multi-Ethnic Study of Atherosclerosis (n=6784).

Results:
After adjustment, higher concentrations of HDL-C (high-density lipoprotein cholesterol), HDL-P (HDL particles), large HDL-P, and apoC3-lacking HDL-C were significantly associated with lower incidence/progression of AVC. Neither small or medium HDL-P nor apoC3-containing HDL-C was significantly associated with AVC incidence/progression. When included together, a significant association was observed only for HDL-C, but not for HDL-P. Secondary analyses showed an inverse relationship between CETP mass, but not activity, and AVC incidence/progression. In exploratory assessments, inverse associations for HDL-C, HDL-P, large HDL-P, and apoC3-lacking HDL with AVC incidence/progression were more pronounced for older, male, and White participants. ApoC3-containing HDL-C only showed a positive association with AVC in these subgroups.

Conclusions:
In a multiethnic population, HDL-C, HDL-P, large HDL-P, and apoC3-lacking HDL-C were inversely associated with long-term incidence and progression of AVC. Further investigation of HDL composition and mechanisms could be useful in understanding pathways that slow AVC.
Caregiver burden experiences of caregivers of patients with schizophrenia: A qualitative inquiry
Authors: Kalayci Erdinç , Uzunaslan İmran , Uzunaslan Şerif 
Published: August 2022

Background: Parents of children with schizophrenia struggle with emotional, social, and economic burdens because they do not receive adequate support and experience difficulties. Aim: To determine the caregiver burden experiences of parents who care for schizophrenic patients and to provide in-depth data on their feelings, thoughts, and opinions on this issue. Methods: In this study, the phenomenological method was used. In-depth interviews were conducted with 13 parents. Maxqda 2020 was used for the analysis of the research data. Results: In our qualitative study, it was concluded that caregivers were stigmatized by their environment, exposed to social isolation, and stigmatized themselves. It has been determined that the social isolation experienced by the parents negatively affects them economically, socially, and emotionally. Conclusion: The results of this study were discussed within the framework of three themes: emotional burden, social burden, and economic burden experienced by caregivers.
Epilepsy and Driving: Attitudes and Practices among Patients Attending a Seizure Clinic
Authors: Dickey William , Morrow James I 
Published: August 2022

Although the loss of freedom to drive is a serious consequence of the diagnosis of epilepsy, it is unclear how well current regulations are understood and adhered to by patients. Using questionnaires completed anonymously, we assessed attitudes and practices among 104 patients with epilepsy. Seventeen (16%) patients were driving, three illegally. In total, eight (8%) patients had at some stage driven illegally, even though seven admitted to having been warned not to do so. Even among the 14 patients currently driving and eligible to do so, only eight (57%) had informed the licensing authority and six (43%) their insurers. Only 34 (33%) patients showed satisfactory knowledge of current regulations, including seven (50%) of those currently driving and 21 (50%) of 42 patients who expressed a wish to drive in the future. Of these 34, only 14 (41%) expressed complete agreement with the regulations. Thus, a significant proportion of patients with epilepsy has driven illegally or has failed to inform the licensing authority or insurers. Understanding of regulations is poor. Less stringent restrictions have been shown to be safe in other countries and might improve compliance.
Temporary Prostatic Stenting and Androgen Suppression: A New Minimally Invasive Approach to Malignant Prostatic Retention
Authors: Anson K M , Barnes D G , Briggs T P , Watson G M , Miller R A 
Published: August 2022

Urinary retention secondary to carcinoma of the prostate is usually treated by ‘channel’ transurethral resection of the prostate either performed alone or in combination with hormone manipulation. The combination of temporary prostatic stenting and androgen suppression may reduce the morbidity and mortality associated with this treatment. We report on our initial experience using the combination of a temporary prostatic stent with the oral anti-androgen Flutamide in 10 patients with urinary retention or severe bladder outflow obstruction secondary to prostatic carcinoma. Eight of the ten patients successfully voided and maintained normal voiding after stent removal. There were two treatment failures requiring prostatic resection. We believe the cost of stenting and medication is entirely justified by patient preference and clearance of hospital beds.
Sport-Related Sudden Natural Death in the City of Birmingham
Authors: Whittington R M , Banerjee A 
Published: August 2022

We undertook a prospective study of all consecutive deaths reported to the Coroner for Birmingham and Solihull in a 5 year period. We identified 52 sudden deaths associated with symptoms commencing during sport participation. We studied the characteristics of these individuals. The majority had been performing at accustomed levels of activity without symptoms for several years. The extrapolation of our findings to preventive strategies remains unclear but we wish to highlight the importance of recognizing premonitory effort-related symptoms.
Outcome of Nasal Layer Reinforcement With Autologous Dermis in Cleft Palate Repair on Postoperative Fistula Formation
Authors: Khan Subhendu , John Jerry R. , Sharma Ramesh K. 
Published: August 2022

Palatal fistulae are challenging complications following cleft palate repair. The addition of acellular dermal matrix (ADM) to cleft palate repair has been shown to reduce fistula formation in previous studies. The use of autologous dermal graft has all the structural advantages of ADM, has less rejection and immunogenic potential, and is cost effective. A prospective study. Patients with Group II and III cleft palate (Nagpur Classification) without prior intervention for palatal repair in the Department of Plastic Surgery at PGIMER from January 2020 till June 2021. The addition of autologous dermal graft for palatoplasty. Outcome of the study was fistula development or exposure of dermal graft. Autologous dermal graft was harvested of average dimension of 8.73 cm2 (range 5.25-18 cm2) from groin region. Sixteen patients were included in the study. Among them, 2 patients (12.5%) developed postoperative fistula (Type III &V Pittsburgh Classification). Our study showed that the rates of postoperative fistula formation are comparable with prior literature using artificial dermal matrices.
Safety and Efficacy Study of Neoadjuvant Radiohormonal Therapy for Oligometastatic Prostate Cancer: Protocol of an Open-Label, Dose-Escalation, Single-Centre Phase I/II Clinical Trial
Authors: Zhao Xianzhi , Xiao Yu-Tian , Yang Yue , Ye Yusheng , Chang Yifan , Jiang Lingong , Eftekhar Md , Ren Shancheng , Zhang Huojun 
Published: August 2022

Background The optimal treatment for oligometastatic prostate cancer (OMPC) is still on its way. Accumulating evidence has proven the safety and feasibility of radical prostatectomy and local or metastasis-directed radiotherapy for oligometastatic patients. The aim of this trial is to demonstrate the safety and feasibility outcomes of metastasis-directed neoadjuvant radiotherapy (naRT) and neoadjuvant androgen deprivation therapy (naADT) followed by robotic-assisted radical prostatectomy (RARP) for treating OMPC. Methods The present study will be conducted as a prospective, open-label, dose-escalation, phase I/II clinical trial. The patients with oligometastatic PCa will receive 1 month of naADT, followed by metastasis-directed radiation and abdominal or pelvic radiotherapy. Then, radical prostatectomy will be performed at intervals of 4-8 weeks after radiotherapy, and ADT will be continued for 2 years. The primary endpoints of the study are safety profiles, assessed by the Common Terminology Criteria for Adverse Events (CTCAE) 5.0 grading scale, and perioperativemorbidities, assessed by the Clavien-Dindo classification system. The secondary endpoints include positive surgical margin (pSM), biochemical recurrence-free survival (bPFS), radiological progression-free survival (RPFS), postoperative continence, and quality of life (QoL) parameters. Discussion The optimal treatment for OMPC is still on its way, prompting investigation for novel multimodality treatment protocol for this patient population. Traditionally, radical prostatectomy has been recommended as one of the standard therapies for localized prostate cancer, but indications have expanded over the years as recommended by NCCN and EAU guidelines. RP has been carried out in some centres for OMPC patients, but its value has been inconclusive, showing elevated complication risks and limited survival benefit. Neoadjuvant radiotherapy has been proven safe and effective in colorectal cancer, breast cancer and other various types of malignant tumors, showing potential advantages in terms of reducing metastatic stem-cell activity, providing clinical downstaging, and reducing potential intraoperative risks. Existing trials have shown that naRT is well tolerated for high-risk and locally-advanced prostate cancer. In this study, we hope to further determine the optimal irradiation dose and patient tolerance for genitourinary, gastrointestinal and systemic toxicities with the design of 3+3 dose escalation; also, final pathology can be obtained following RP to further determine treatment response and follow-up treatment plans. Trial registration Chinese Clinical Trial Registry, ChiCTR1900025743. http://www.chictr.org.cn/showprojen.aspx?proj=43065 .
Have We Got a Deal for You: Do You Want the Good News or Bad News First?
Authors: Wakefield Kirk L. , Raghubir Priya , Inman J. Jeffrey 
Published: August 2022

Traditional practice prominently presents offers (e.g., “50% Off”) followed by a quantity (“When you buy two”), duration (“Today only”), or other conditional restriction as a scarcity appeal to increase urgency. Placing a hurdle to clear before purchase eligibility presents the good news of the offer followed by the bad news of the restriction. We propose and test a sales promotion framework for admission-based experiences showing that leading with the bad news first (the restriction) followed by the good news (the discount) is consistent with consumer news order preferences and changes perceptions of the deal. Our first study confirms consumer preference for bad news before good news in general and ticket offers in particular. The next two studies examine the process by which leading with the bad news (of the restriction first, discount later) increases the salience of the deal (% off). This in turn makes the customer feel in greater control over the offer, thereby making the deal appear to be fairer and more attractive, leading to increased purchase intentions. A fourth study in the field shows presenting the restriction followed by a discount improves click-through and potential revenue compared to presenting the identical offer with the discount preceding the restriction.
Investigation of the Antinociceptive Activity of the Hydroethanolic Extract of Junglas nigra Leaf by the Tail-Immersion and Formalin Pain Tests in Rats
Authors: Srebro Dragana , Rajković Katarina , Dožić Branko , Vujović Katarina Savić , Brkić Branislava Medić , Milić Petar , Vučković Sonja 
Published: August 2022

Background Juglans (J.) nigra leaf is obtained from a plant that is used in traditional medicine in some countries to alleviate inflammatory diseases. Aim The aim of this study was to compare the effects of J. nigra extract on acute nociceptive and inflammatory pain in rats. Methods Antinociceptive activity was examined in Wistar rats by the tail-immersion and formalin tests. Motor function was assessed using the rotarod test. Plant extract was administered intraperitoneally. Results In the tail-immersion test, the maximal antinociceptive effect of the plant extract (100–330 mg/kg) was about 24–30% and is the result of the effect of a high concentration of ethanol. In the formalin test, the plant extract (41.3–330 mg/kg) significantly and dose-dependently inhibited nociception in both phases of the test with similar maximal effects of about 76% and 85%. Only the plant extract at the dose of 330 mg/kg caused a significant time-dependent reduction in time spent on the rotarod. Conclusions In rats, the preventive systemic administration of the hydroethanolic extract of J. nigra leaf reduced chemically but not thermally induced pain. Higher efficacy was obtained in pain associated with inflammation and tissue injury. The antinociceptive effect is dose-dependent and may be limited by motor impairment.
Phenakite and bertrandite: products of post-magmatic alteration of beryl in granitic pegmatites (Tatric Superunit, Western Carpathians, Slovakia)
Authors: Uher Pavel , Ozdín Daniel , Bačík Peter , Števko Martin , Ondrejka Martin , Rybnikova Olena , Chládek Štěpán , Fridrichová Jana , Pršek Jaroslav , Puškelová Ľubica 
Published: August 2022

AbstractThe beryllium silicate minerals phenakite and bertrandite have been identified in granitic pegmatite dykes of the beryl-columbite subtype of Variscan age (~340−355 Ma), associated with S- to I-type granitic rocks of the Tatric Superunit, Western Carpathians (Slovakia). The two beryllium silicates and associated minerals were characterised by electron microprobe analysis, back-scattered electron petrography and cathodoluminescence imagery, X-ray diffraction and micro-Raman techniques. Phenakite and bertrandite form euhedral-to-anhedral crystals and aggregates in irregular domains and veinlets replacing primary magmatic beryl. A detailed textural study revealed a close genetic association of phenakite and bertrandite with secondary fine-grained quartz, K-feldspar and muscovite. Locally, clay phyllosilicate minerals, (with compositions similar to those of Fe-dominant hydrobiotite, beidellite, nontronite and saponite) occur as the youngest minerals. During the post-magmatic (hydrothermal) stage of the pegmatites, infiltration of aqueous K-bearing fluids atT≈ 200–400°C resulted in the breakdown of magmatic beryl to secondary assemblages containing phenakite and bertrandite.
Immunothrombosis and vascular heterogeneity in cerebral cavernous malformation
Authors: Globisch Maria A. , Onyeogaziri Favour C. , Jauhiainen Suvi , Yau Anthony C. Y. , Orsenigo Fabrizio , Conze Lei L. , Arce Maximiliano , Corada Monica , Smith Ross O. , Rorsman Charlotte , Sundell Veronica , Fernando Dinesh , Daniel Geoffrey , Mattsson Oscar , Savander Henri , Wanders Alkwin , Rezai Jahromi Behnam , Laakso Aki , Niemelä Mika , Dejana Elisabetta , Magnusson Peetra U. 
Published: August 2022

Abstract
Cerebral cavernous malformation (CCM) is a neurovascular disease that results in various neurological symptoms. Thrombi have been reported in surgically resected CCM patient biopsies, but the molecular signatures of these thrombi remain elusive. Here, we investigated the kinetics of thrombi formation in CCM and how thrombi affect the vasculature and contribute to cerebral hypoxia. We used RNA sequencing to investigate the transcriptome of mouse brain endothelial cells with an inducible endothelial-specific Ccm3 knock-out (Ccm3-iECKO). We found that Ccm3-deficient brain endothelial cells had a higher expression of genes related to the coagulation cascade and hypoxia when compared with wild-type brain endothelial cells. Immunofluorescent assays identified key molecular signatures of thrombi such as fibrin, von Willebrand factor, and activated platelets in Ccm3-iECKO mice and human CCM biopsies. Notably, we identified polyhedrocytes in Ccm3-iECKO mice and human CCM biopsies and report it for the first time. We also found that the parenchyma surrounding CCM lesions is hypoxic and that more thrombi correlate with higher levels of hypoxia. We created an in vitro model to study CCM pathology and found that human brain endothelial cells deficient for CCM3 expressed elevated levels of plasminogen activator inhibitor-1 and had a redistribution of von Willebrand factor. With transcriptomics, comprehensive imaging, and an in vitro CCM preclinical model, this study provides experimental evidence that genes and proteins related to the coagulation cascade affect the brain vasculature and promote neurological side effects such as hypoxia in CCMs. This study supports the concept that antithrombotic therapy may be beneficial for patients with CCM.
Insular functional connectivity in migraine with aura
Authors: Gollion Cédric , Lerebours Fleur , Nemmi Federico , Arribarat Germain , Bonneville Fabrice , Larrue Vincent , Péran Patrice 
Published: August 2022

AbstractIntroductionInsula plays an integrating role in sensory, affective, emotional, cognitive and autonomic functions in migraine, especially in migraine with aura (MA). Insula is functionally divided into 3 subregions, the dorsoanterior, the ventroanterior and the posterior insula respectively related to cognition, emotion, and somatosensory functions. This study aimed at investigating functional connectivity of insula subregions in MA.MethodsTwenty-one interictal patients with MA were compared to 18 healthy controls (HC) and 12 interictal patients with migraine without aura (MO) and were scanned with functional MRI during the resting state. Functional coupling of the insula was comprehensively tested with 12 seeds located in the right and left, dorsal, middle, ventral, anterior and posterior insula, by using a seed-to-voxel analysis.ResultsSeed-to-voxel analysis revealed, in MA, a strong functional coupling of the right and left antero-dorsal insula with clusters located in the upper cerebellum. The overlap of these cerebellar clusters corresponded to the vermis VI. These functional couplings were not correlated to duration of MA, frequency of MA attacks nor time since last MA attack, and were not found in MO.DiscussionThe anterior insula and superior cerebellum, including vermis VI, are components of the central Autonomic Nervous System (ANS) network. As these regions are involved in the control of cardiovascular parasympathetic tone, we hypothesize that this connectivity may reflect the cardiovascular features of MA.ConclusionThe anterior dorsal insula is connected with vermis VI in MA patients in the resting state. This connectivity may reflect the cardiovascular features of MA.Trial registrationNCT02708797.
Length-Dependent Photoelectric Property of ZnO Nanowires
Authors: Ren Ren , Ren Xiaomin , Liu Hao , Huang Yongqing , Yuan Weifang 
Published: August 2022

AbstractAn interesting phenomenon that the photocurrent (the difference between illumination and dark current) of a ZnO nanowire (NW) under a specified voltage increased as its length increased in a certain range was observed previously and it was supposed to be mainly due to a special mean free path effect (MFPE) which caused a special distribution of dark electron density along the length with two higher electron density regions near the two ends of the NW, respectively, and the lower one in the middle part. However, such an explanation would be unreasonable and the true reasons should be the growing-process caused variation of the oxygen adsorption capacity along the NW length and the length-dependent lifetime of photogenerated carriers. Based on this understanding, a theoretical model to properly explain this phenomenon is proposed and the calculation results are in good agreement with the experimental data. This work has introduced an improved insight into the theory of the length-dependent photoelectric property of ZnO NWs.