Controversial Literature Research Articles

“Special Feature: The Achievements of John Dennis,” ed. Claude Willan. 1650–1850: Ideas, Aesthetics, and Inquiries in the Early Modern Era, ed. Kevin L. Cope

“Special Feature: The Achievements of John Dennis,” ed. Claude Willan. <i>1650–1850: Ideas, Aesthetics, and Inquiries in the Early Modern Era, ed. Kevin L. Cope</i>

Increase of blood neuregulin 4 is associated with type 2 diabetes mellitus and hypertension in obese patients

Obesity and type 2 diabetes mellitus (T2DM) are global epidemics at the present time, being a serious public health issue. An increased prevalence in the number of obese people promotes a risk for developing cardiovascular diseases (CVD) and some types of cancer. The ErbB signaling pathway plays a significant role in development of the disorders associated with metabolic dysfunction (e.g., T2DM, obesity, arterial hypertension). Neuregulin 4 (NRG4) is a new adipokine with similar effects to adiponectin. Interaction between the ErbB3, ErbB4 receptors and their ligand, NRG4, launches the processes required to maintain the energy balance in the cells. There are controversial literature data on NRG4 levels in blood circulation. In particular, the existing data concerning functions / mechanism of NRG4 action has been obtained in experimental animals and cell lines, which is not always reproducible in humans. According to some works, liver may be the key target organ for NRG4. The present article is devoted to assessment of relationships between the NRG4 level in blood, and the parameters of carbohydrate and lipid metabolism, as well as presence of diseases associated with obesity. The study included obese patients with and without type 2 diabetes. The content of NRG4, indices of carbohydrate and lipid metabolism in the blood was assessed by means of enzyme immunoassay and biochemical techniques, respectively. It was found that the level of NRG4 was increased in obese patients with T2DM compared with healthy donors, and obese patients without T2DM. Statistical evaluation by correlation and regression analysis revealed numerous relationships between NRG4 and the parameters of lipid and carbohydrate metabolism, as well as some correlations between the NRG4 levels and clinical disorders associated with obesity (type 2 diabetes and arterial hypertension). Thus, NRG4 may be involved into the development of dyslipidemia in obese patients. We consider an increase of blood NRG4 levels in obese patients with type 2 diabetes as a compensatory response to the increased insulin-mediated lipogenesis. The data obtained are important in search for new points of influence upon pathogenesis of diseases associated with metabolic disorders. Neuroregulin 4 and its receptors may be promising targets for the treatment of socially significant clinical disorders.

Sedition: The Spread of Controversial Literature and Ideas in France and Scotland, c. 1550–1610. Edited by John O’Brien and Marc Schachter

<i>Sedition: The Spread of Controversial Literature and Ideas in France and Scotland, c. 1550–1610</i>. Edited by John O’Brien and Marc Schachter

Ut unum sint: Constantinople and Rome in Ruthenian Historical Narrations of the Seventeenth Century

As it is broadly known, the history of the Church began to be one of the most potent elements in Early-modern controversial literature. Ruthenian polemical writings were not an exception; both Uniate and Orthodox authors broadly used facts of Church history considering themselves as the continuators of the Kyivan Christianity. Understanding historical narrative as a logically consistent sequence of events with implicit causal relations, this article presents the analysis of the appearance and transformation of two important historical narrations: on a Great Schism and on the Unity of Florence. Both historical narratives were written with polemical purposes and are closely connected with each other. Playing with names, dates, and sources, Ruthenian early-modern intellectuals in more or less skillful ways tried to give a historical overview of the relations between Rus, Constantinople, and Rome.The medieval Byzantine and Slavic polemical traditions were not reliable anymore. A different attitude to historiographical authorities provoked the shift of the hierarchy of the quoted sources. Ruthenian tradition, represented by the hagiographical texts and Russian Chronograph, is mostly quoted by the Uniate authors, not by orthodox ones. For them it is the most important historical proof that their own historical choice — the Union with Rome — does not contradict but continues the faith of their fathers: Kyiv metropolitans of the pre-Mongolian era.

Adjuvant therapy (AT) in patients (pts) with radically resected ampullary adenocarcinoma (AA): A monocentric retrospective analysis.

e16142 Background: Ampullary adenocarcinoma (AA) is a rare tumor. Radical surgery is the only curative treatment for localized AA. The role of AT is not clearly defined and previous evidence in literature is poor and controversial. Hence, we retrospectively analyzed radically resected AA pts at our Institution, investigating the impact of AT on survival and the role of possible prognostic and/or predictive factors. Methods: Radically resected AA pts were retrospectively included in the analysis, divided into two groups: pts receiving AT and pts undergoing only postoperative observation (PO). The following variables were collected: gender; age (≤ 65 vs &gt; 65 years); baseline ECOG PS (0 vs ³ 1); histologic subtype (pancreatobiliary vs intestinal); tumor stage (T1-2 vs T3-4); nodal status (N0 vs N+), margin status (R0 vs R+); radiotherapy (yes vs no), AT regimen [Gemcitabine (GMZ)-based vs fluoropyrimidine (FP)-based treatment)]. The objective of the analysis was to evaluate the impact of AT on overall survival (OS). Univariate and multivariate analyses were performed. Results: From 2007 to 2021, a total of 69 pts with radically resected AA were identified: 41 (59%) pts received AT, 28 (41%) PO. The median age was 65 years (41-81), 42 (61%) were males, ECOG PS was ³ 1 in 45 (65%) pts. Tumor characteristics were: 31 (45%) pancreatobiliary, 26 (38%) intestinal, 9 (13%) mixed subtype and 3 (4%) not available; 41 (59%) pts had T3-T4 stage tumor; 34 (49%) were N+. Out of 41 pts receiving AT, 27 (66%) pts were treated with FP-based AT, 14 (34%) with GMZ-based AT; 16 (23%) pts received also RT. In the overall population, median OS was 59.8 months. At the univariate analysis, there was a statistically significant association of T status with OS (p 0.03), confirmed at multivariate analysis (p 0.03). Further variables (ECOG PS, AT, nodal status and histologic subtype) were not associated with survival. Among the 41 pts receiving AT, median OS was 58.7 months. At the univariate analysis, AT regimen was significantly associated with OS (p 0.02), and it was confirmed at the multivariate analysis. In particular, median OS was 59.8 and 28.3 months in pts receiving FP- and GMZ-based AT, respectively [HR 0.26, (95% CI: 0.09-0.78), p = 0.001]. Conclusions: Among pts with radically resected AA, AT, compared with PO, was not associated with a significant survival benefit. However, among pts receiving AT, FP-based regimen seems to significantly improve OS in comparison to GMZ-based regimen, independently of histologic subtype. Our findings, from a retrospective and limited case series, add to controversial literature data and miss to clarify the real impact of AT in radically resected AA pts. A randomized trial of AT vs PO would provide further information in this setting.

P-155 Adjuvant therapy (AT) in patients (pts) with radically resected ampullary adenocarcinoma (AA): A monocentric retrospective analysis

Ampullary adenocarcinoma (AA) is a rare tumor. Radical surgery is the only curative treatment for localized AA. The role of AT is not clearly defined and previous evidence in literature is poor and controversial. Hence, we retrospectively analyzed radically resected AA pts at our Institution, investigating the impact of AT on survival and the role of possible prognostic and/or predictive factors. Radically resected AA pts were retrospectively included in the analysis, divided into two groups: pts receiving AT and pts undergoing only postoperative observation (PO). The following variables were collected: gender; age (≤ 65 vs > 65 years); baseline ECOG PS (0 vs 3 1); histologic subtype (pancreatobiliary vs intestinal); tumor stage (T1-2 vs T3-4); nodal status (N0 vs N+), margin status (R0 vs R+); radiotherapy (yes vs no), AT regimen [Gemcitabine (GMZ)-based vs fluoropyrimidine (FP)-based treatment)]. The objective of the analysis was to evaluate the impact of AT on overall survival (OS). Univariate and multivariate analyses were performed. From 2007 to 2021, a total of 69 pts with radically resected AA were identified: 41 (59%) pts received AT, 28 (41%) PO. The median age was 65 years (41-81), 42 (61%) were males, ECOG PS was 3 1 in 45 (65%) pts. Tumor characteristics were: 31 (45%) pancreatobiliary, 26 (38%) intestinal, 9 (13%) mixed subtype and 3 (4%) not available; 41 (59%) pts had T3-T4 stage tumor; 34 (49%) were N+. Out of 41 pts receiving AT, 27 (66%) pts were treated with FP- based AT, 14 (34%) with GMZ-based AT; 16 (23%) pts received also RT. In the overall population, median OS was 59.8 months. At the univariate analysis, there was a statistically significant association of T status with OS (p 0.03), confirmed at multivariate analysis (p 0.03). Further variables (ECOG PS, AT, nodal status and histologic subtype) were not associated with survival. Among the 41 pts receiving AT, median OS was 58.7 months. At the univariate analysis, AT regimen was significantly associated with OS (p 0.02), and it was confirmed at the multivariate analysis. In particular, median OS was 59.8 and 28.3 months in pts receiving FP- and GMZ-based AT, respectively [HR 0.26, (95% CI: 0.09-0.78), p = 0.001]. Among pts with radically resected AA, AT, compared with PO, was not associated with a significant survival benefit. However, among pts receiving AT, FP-based regimen seems to significantly improve OS in comparison to GMZ- based regimen, independently of histologic subtype. Our findings, from a retrospective and limited case series, add to controversial literature data and miss to clarify the real impact of AT in radically resected AA pts. A randomized trial of AT vs PO would provide further information in this setting.

Sedition. The Spread of Controversial Literature and Ideas in France and Scotland, c. 1550–1610, by J. O’Brien and M. Schachter (Eds.)

Sedition. The Spread of Controversial Literature and Ideas in France and Scotland, c. 1550–1610, by J. O’Brien and M. Schachter (Eds.)

Can visual capture of sound separate auditory streams?

In noisy contexts, sound discrimination improves when the auditory sources are separated in space. This phenomenon, named Spatial Release from Masking (SRM), arises from the interaction between the auditory information reaching the ear and spatial attention resources. To examine the relative contribution of these two factors, we exploited an audio-visual illusion in a hearing-in-noise task to create conditions in which the initial stimulation to the ears is held constant, while the perceived separation between speech and masker is changed illusorily (visual capture of sound). In two experiments, we asked participants to identify a string of five digits pronounced by a female voice, embedded in either energetic (Experiment 1) or informational (Experiment 2) noise, before reporting the perceived location of the heard digits. Critically, the distance between target digits and masking noise was manipulated both physically (from 22.5 to 75.0 degrees) and illusorily, by pairing target sounds with visual stimuli either at same (audio-visual congruent) or different positions (15 degrees offset, leftward or rightward: audio-visual incongruent). The proportion of correctly reported digits increased with the physical separation between the target and masker, as expected from SRM. However, despite effective visual capture of sounds, performance was not modulated by illusory changes of target sound position. Our results are compatible with a limited role of central factors in the SRM phenomenon, at least in our experimental setting. Moreover, they add to the controversial literature on the limited effects of audio-visual capture in auditory stream separation.

Atomic Metaphors, Victims, and the Contestations of Nuclear Discourse

Atomic metaphors permeated daily life as the world reacted to the atomic bombings of Japan and the nuclear threat of the Cold War. These metaphors reveal a widespread sense of ownership of atomic narratives and public conceptions of victimhood that are often divorced from actual nuclear victims. Japan faced the reality of the nuclear again in 2011 when three reactors at the Fukushima Daiichi Nuclear Power Plant exploded, spreading toxic radiation far and wide. Rather than turn to religion to make sense of the traumatic destruction and existential threat of this invisible force, the Japanese have processed the catastrophe through a secular discussion of victimhood. In the decade since the Fukushima accident, the discourse about victims in Japan has narrowed to emphasize the authority of the tōjisha—victims with direct experience of the disaster—to tell their story. The debate over narrative ownership has challenged the literary community, and post-disaster Japanese literature is an important site of imaginative exploration of this victimhood. Using the theories of Jean-Luc Nancy and Michael Rothberg, this article examines collective memory and the catastrophic equivalence of Hiroshima and Fukushima, as well as the Japanese terminology for victims, in order to provide insight into the struggles for ownership of atomic narratives. Rather than proposing solutions, the article interrogates the ongoing literary controversy over the victim/non-victim divide.

METHODS FOR ORTHOPEDIC TREATMENT OF PATIENTS WITH DECLINED CLINICAL CROWNS OF SUPPORTING TEETH. LITERATURE REVIEW

Abstract. The presence of a decayed tooth is a fairly common problem with which patients go to the dentist. The question of preserving such teeth remains controversial today, both in domestic and foreign specialized literature. Biomechanical complications in the restoration of destroyed teeth at the moment remain one of the most important problems of modern restoration and orthopedic dentistry. A number of authors regard the destruction of the tooth crown as a cause that eventually leads to a violation of the morpho functional unity of the dentition and the pathological state of the entire dental system. In addition, the reasons for the destruction of the clinical crown of teeth are presented, including: caries and its complications, non-carious processes. The strength of the tooth decreases in proportion to the loss of the crown part tissue due to diseases of the hard tissues of the tooth and restoration treatment. Special attention is paid to the condition of the dentin, which changes its structure due to the presence of cracks or physical changes, which is the result of excessive load on the hard tissues of the tooth. This article analyzes the literature sources of domestic and foreign origin, reflecting the methods of treatment of a destroyed clinical tooth crown. Since the final result of tooth restoration should be an aesthetic form and function, special attention should be paid to preserving the maximum volume of tooth tissues using minimally invasive organ-preserving techniques. It is established that the degree of destruction of the crowns of teeth determines the amount of intervention, the choice of design, restoration technology and structural material. Early diagnosis of the degree of destruction of the crowns of teeth and knowledge of the pathogenesis of possible complications after tooth extraction are of great importance, which determines the scope of intervention, the choice of design and restoration technology.

The Münster Rising, Memories of Violence, and Perceptions of Dissent in Restoration England

AbstractThis article examines the ways in which the violent Anabaptist rising at Münster in 1533–5 was reinterpreted in Restoration England. Historians have often recognized that the incident was used to attack English Baptists in the seventeenth century, but there has been little systematic exploration of the processes behind this. This article suggests that recollections of Münster in later seventeenth-century England were a species of ‘cosmopolitan memory’ – an internationally shared memory of trauma put to distinctive local uses. References to Münster served as ways for English writers to tie nonconformists to specific acts of religious violence in England, including the Civil Wars and Thomas Venner's 1661 rising in London, without directly recalling these events. Historical discussions of the Münster rising therefore often directly transformed German Anabaptists into Quakers or Fifth Monarchists. Condemnations of the violence in the German city were also used by Congregationalists and Presbyterians to differentiate themselves from Baptists and Quakers and to emphasize their orthodoxy. Some Baptist writers responded by disclaiming their links to continental Anabaptists, while others moved to question the established historiography around the Münster rising. This article demonstrates these points through a range of sources, including sermons, letters, commentaries, controversial literature, and almanacs.

Prognostic assessment of different methods for eosinophils detection in oral tongue cancer

AbstractBackgroundTATE has been proposed as a prognostic factor in oral cancer staging; however, the controversial literature data limit its application in the routine diagnosis. The aim of this study was to evaluate the prognostic value of TATE in patients with oral tongue cancer. The second aim was to identify any difference in the methods of eosinophil quantification or in the cutoff values reported in literature.MethodsClinic‐pathological data of 204 patients treated at “Ospedali Riuniti” Hospital, Ancona, Italy, were collected. Evaluation of TATE was performed on hematoxylin‐and‐eosin‐stained slides and correlation with survival outcomes was evaluated. The number of eosinophils per square millimeter was evaluated by using two methods, namely density (TATE‐1) and classical (TATE‐2) methods. For each of the 2 methods tested, patients were stratified into two or three groups, according to the most used cutoff values reported in literature.ResultsRegardless of the method of eosinophil quantification or the cutoff values used, patients with high TATE had a significantly better disease‐specific survival. The density method (TATE‐1) showed a better predictive performance, in particular when applying a single cutoff of 67 eosinophils/mm2, two cutoffs of 10 and 100 eosinophils/mm2, or two cutoffs of 50 and 120 eosinophils/mm2.ConclusionThe evaluation of TATE is simple, cost‐effective, and easy to implement in daily practice with the aim of improving risk stratification of patients affected by oral tongue cancer. Results of prognostic performance analysis suggest using density (TATE‐1) method as the standard approach to evaluate TATE in future studies, enhancing replicability.

The role of lexical homogeneity in the poetry rhythm of Hazin Lahiji

Hazin Lahiji is one of the prominent poets of the twelfth century AH (1103-1180). A poet who has been the center of many literary controversies and conflicts of his time, he is also a rhythm and a criterion for measuring the poems of his contemporaries, and the so-called "corrector", he has personality that Indian grandee are proud to talk to him. The aim of this writing, with attention to the homogeneity of words in creating rhythm and integration into poetry and with analytical-descriptive method, and with formalistic approach; is to show how Hazin Lahiji creates the most rhythm from the beauties of rhetorical industries and the aspect of their order and coherence in their proper place and time, and how to connect the rhythm of poetry with other elements, in order to add value to the sound and music of poems. And he uses a kind of understanding between his thought and sympathy with the audience to show the distinctive poetic language. To explain this issue, he organized disciplines under two general categories "imperfect” and "perfect balance" and examined the role of industries related to each category as a process of de-familiarization through the music of Hazin (sad) poems. The present study shows that Hazin Lahiji, with the knowledge of the aesthetic aspects of word music, has been able to affect the soul and spirit of the audience by all kinds of repetition and observing the appropriateness of words and choosing beautiful words in the right place, and to express himself poetically as much as possible and to release his words from the usual hierarchy and linearity.

MTHFR C677T and A1298C Polymorphisms in Breast Cancer, Gliomas and Gastric Cancer: A Review.

Folate (vitamin B9) is found in some water-soluble foods or as a synthetic form of folic acid and is involved in many essential biochemical processes. Dietary folate is converted into tetrahydrofolate, a vital methyl donor for most methylation reactions, including DNA methylation. 5,10-methylene tetrahydrofolate reductase (MTHFR) is a critical enzyme in the folate metabolism pathway that converts 5,10-methylenetetrahydrofolate into 5-methyltetrahydrofolate, which produces a methyl donor for the remethylation of homocysteine to methionine. MTHFR polymorphisms result in reduced enzyme activity and altered levels of DNA methylation and synthesis. MTHFR polymorphisms have been linked to increased risks of several pathologies, including cancer. Breast cancer, gliomas and gastric cancer are highly heterogeneous and aggressive diseases associated with high mortality rates. The impact of MTHFR polymorphisms on these tumors remains controversial in the literature. This review discusses the relationship between the MTHFR C677T and A1298C polymorphisms and the increased risk of breast cancer, gliomas, and gastric cancer. Additionally, we highlight the relevance of ethnic and dietary aspects of population-based studies and histological stratification of highly heterogeneous tumors. Finally, this review discusses these aspects as potential factors responsible for the controversial literature concerning MTHFR polymorphisms.

Reduced graphene oxide-ZnO hybrid composites as photocatalysts: The role of nature of the molecular target in catalytic performance

Spurred by controversial literature findings, we enwrapped reduced graphene oxide (rGO) in ZnO hierarchical microstructures (rGO loadings spanning from 0.01 to 2 wt%) using an in situ synthetic procedure. The obtained hybrid composites were carefully characterized, aiming at shining light on the possible role of rGO on the claimed increased performance as photocatalysts. Several characterization tools were exploited to unveil the effect exerted by rGO, including steady state and time resolved photoluminescence, electron microscopies and electrochemical techniques, in order to evaluate the physical, optical and electrical features involved in determining the catalytic degradation of rhodamine B and phenol in water.Several properties of native ZnO structures were found changed upon the rGO enwrapping (including optical absorbance, concentration of native defects in the ZnO matrix and double-layer capacitance), which are all involved in determining the photocatalytic performance of the hybrid composites. The findings discussed in the present work highlight the high complexity of the field of application of graphene-derivatives as supporters of semiconducting metal oxides functionality, which has to be analyzed through a multi-parametric approach.

Left atrial appendage morphology and the risk of stroke

Abstract In patients with non-valvular atrial fibrillation (AF) the risk of stroke is five times higher than in patients with sinus rhythm. Moreover, stroke is likely to be more severe in the AF patient population. Left atrial appendage (LAA) is the most common source of emboli in AF-related stroke. LAA thrombus is present in 15% of AF patients. Therefore, numerous studies aimed to evaluate the role of LAA structure and function in stroke formation. Higher LAA volume and bigger LAA orifice have been reported to be associated with increased risks of stroke. Moreover, not only the size, but also the shape of the LAA influences thrombus formation. The presence of an obvious bend in the proximal part of the dominant LAA lobe, described as chicken wing LAA morphology has been reported to be protective against stroke. However, other studies are not consistent with this finding and there is no consensus about LAA morphology categories. LAA has reservoir, contractile, electric and endocrine functions, that can provide essential information about the risk of clot formation and embolic events. Decreased LAA flow velocity, reflecting lower LAA contractility has been described to be associated with higher stroke risk. All in all, even if the LAA plays an important role in stroke formation, there are controversial literature data, therefore further studies are needed to evaluate the underlying mechanisms.

(NE)SUPRANTAMASIS VYDŪNAS: BALIO SRUOGOS, JULIJONO LINDĖS-DOBILO IR VYDŪNO LITERATŪRINĖ POLEMIKA

The article seeks to emphasize peculiarity of reception of the oeuvre of Prussian Lithuanian philosopher and writer Vydūnas. The author represents analysis of the literary polemic between Lithuanian writers Balys Sruoga and Julijonas Lindė-Dobilas. This polemic arose from B. Sruoga’s sharp review written for Vydūnas’s mystery play Jūrų varpai. Subsequently Vydūnas involves himself in to polemic with B. Sruoga which developed into direct literary controversy. The article discusses not only question about intricacy of Vydūnas’s works but seeks to answer the question: why B. Sruoga rejects professional critical evaluation of the play and insistently holds an opinion that Vidūnas’s oeuvre is unacceptable for Lithuanian reader. The article also introduces how after a few years changed B. Sruoga’s attitude in respect to Vydūnas’s personality and his oeuvre.

Mesoamerican Nephropathy (MeN): What We Know so Far.

In 2002, a report from El Salvador described a high incidence of chronic kidney disease (CKD) of unknown cause, mostly in young males from specific coastal areas. Similar situations were observed along the Pacific Ocean coastline of other Central American countries and southern Mexico (Mesoamerica). This new form of CKD has been denominated Mesoamerican endemic nephropathy (MeN). The typical presentation of MeN is a young male from an endemic area with a family history of CKD, low eGFR, high serum creatinine, low level of albuminuria, hypokalemia, hyperuricemia, and urine urate crystals. Kidney biopsy demonstrating tubulointerstitial nephritis remains the gold standard for diagnosis but is available only for a minority. Commonly proposed causes include thermal stress/dehydration and/or exposure to environmental pollutants. However, likely, a third factor, which could be genetic or epigenetic, could contribute to the cause and development of the disease, along with social determinants. Currently, preventive measures focus on minimizing workers exposure to thermal stress/dehydration. There are many research opportunities and priorities should include clinical trials to evaluate the efficacy and safety of the current treatment protocols, along with etiological and genetic studies, and the development of kidney disease data systems. Although there is scant and controversial literature with regard s to the etiology, diagnosis and management of the disease, our aim is to provide the reader a vision of the disease based on our experience.

A Reflection on Controversial Literature on Screen Time and Educational Apps Use in 0-5 Years Old Children.

Over the last five years, there has been a significant increase in screen time and apps usage by children under five years old. The considerable growth in usage by very young children has not corresponded to conclusive and consistent research investigating its possible benefits and risks. This article proposes a brief overview of recent results in this field, specifically focusing on the use of educational apps and their positive, null, and/or negative outcomes on young children’s cognitive, emotional, and behavioral functioning. The aim of the present article is to stimulate the development and advancement of evidence-based guidelines that caregivers and educators could adopt to regulate very young children’s engagement with digital technologies.

To trigger or not to trigger ovulation in a natural cycle for frozen embryo transfer: a randomized controlled trial.

Is the clinical pregnancy rate (CPR) following a frozen embryo transfer (FET) in a natural cycle (NC) higher after spontaneous ovulation than after triggered ovulation [natural cycle frozen embryo transfer (NC-FET) versus modified NC-FET]? The CPR did not vary significantly between the two FET preparation protocols. Although the use of FET is continuously increasing, the most optimal endometrial preparation protocol is still under debate. For transfer in the NC specifically, conflicting results have been reported in terms of the outcome following spontaneous or triggered ovulation. In a tertiary hospital setting, subjects were randomized with a 1:1 allocation into two groups between January 2014 and January 2019. Patients in group A underwent an NC-FET, while in group B, a modified NC-FET was performed with a subcutaneous hCG injection to trigger ovulation. In neither group was additional luteal phase support administered. All embryos were vitrified-warmed on Day 3 and transferred on Day 4 of embryonic development. The primary outcome was CPR at 7weeks. All patients were followed further until 10weeks of gestation when the ongoing pregnancy rate (OPR) was defined by the observation of foetal cardiac activity on ultrasound scan. Other secondary outcomes included biochemical pregnancy rate, early pregnancy loss and the number of visits, blood samples and ultrasonographic examinations prior to FET. A total of 260 patients (130 per study arm) were randomized, of whom 12 withdrew consent after study arm allocation. A total of 3 women conceived spontaneously before initiating the study cycle and 16 did not start for personal or medical reasons. Of the 229 actually commencing monitoring for the study FET cycle, 7 patients needed to be switched to a hormonal replacement treatment protocol due to the absence of follicular development, 12 had no embryo available for transfer after warming and 37 had a spontaneous LH surge before the ovulation trigger could be administered, although they were allocated to group B. Given the above, an intention-to-treat (ITT) analysis was performed taking into account 248 patients (125 in group A and 123 in group B), as well as a per protocol (PP) analysis on a subset of 173 patients (110 in group A and 63 in group B). Demographic features were evenly distributed between the study groups, as were the relevant fresh and frozen ET cycle characteristics. According to the ITT analysis, the CPR and OPR in group A (33.6% and 27.2%, respectively) and group B (29.3% and 24.4%, respectively) did not vary significantly [relative risk (RR) 0.87, 95% CI (0.60;1.26), P= 0.46 and RR 0.90, 95% CI (0.59;1.37), P= 0.61, respectively]. Biochemical pregnancy rate and early pregnancy loss were also found to be not statistically significantly different between the groups. In contrast, more clinic visits and blood samplings for cycle monitoring were required in the NC-FET group (4.05 ± 1.39) compared with the modified NC-FET group (3.03 ± 1.16, P= <0.001), while the number of ultrasound scans performed were comparable (1.70 ± 0.88 in group A versus 1.62 ± 1.04 in group B). The additional PP analysis was in line with the ITT results: CPR in group A was 36.4% versus 38.1% in group B [RR 1.05, 95% CI (0.70;1.56), P= 0.82]. The results are limited by the high drop-out rate for the PP analysis in the modified NC-FET group as more than one-third of the subjects allocated to this group ovulated spontaneously before ovulation triggering. Nonetheless, this issue is inherent to routine clinical practice and is an important observation of an event that can only be avoided by performing a very extensive monitoring that limits the practical advantages associated with modified NC-FET. Furthermore, although this is the largest randomized controlled trial (RCT) investigating this specific research question so far, a higher sample size would allow smaller differences in clinical outcome to be detected, since currently they may be left undetected. This RCT adds new high-quality evidence to the existing controversial literature concerning the performance of NC-FET versus modified NC-FET. Based on our results showing no statistically significant differences in clinical outcomes between the protocols, the treatment choice may be made according to the patient's and treating physician's preferences. However, the modified NC-FET strategy reduces the need for hormonal monitoring and may therefore be considered a more patient-friendly and potentially cost-effective approach. No specific funding was available for this study. None of the authors have a conflict of interest to declare with regard to this study. NCT02145819. 8 January 2014. 21 January 2014.