bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of strict COVID-19 lockdown on patients with obsessive-compulsive disorder compared to a clinical and a nonclinical sample
Authors: D’Urso Giordano , Magliacano Alfonso , Dell’Osso Bernardo , Lamberti Hekla , Luciani Adalgisa , Mariniello Teresa S. , Pomes Mattia V. , Rifici Lorenza M. ,   The COVID in OCD Study Group, Iasevoli Felice , de Bartolomeis Andrea 
Published: June 2023

Abstract

Background
Symptoms of obsessive-compulsive disorder (OCD) have been reported to increase during the COVID-19 lockdowns because of the hygiene requirements related to the pandemic. Patients with adjustment disorder (AD) may, in turn, represent a vulnerable population for identifiable stressors. In this study, we aimed at assessing potential symptoms changes in OCD patients during the lockdown in comparison with AD patients as well as versus healthy controls (HC).

Methods
During the COVID-related lockdown, we enrolled 65 patients and 29 HC. Participants were tested with four clinical rating scales (Yale–Brown obsessive-compulsive scale and Brown Assessment of Beliefs Scale for OCD patients; Beck Depression Inventory-II and State–Trait Anxiety Inventory-Y for each group) that had been also administered just before the Italian lockdown.

Results
Our results showed that during the lockdown: (i) the symptoms of depression and anxiety increased in all groups, but this increase was most pronounced in HC (p < 0.001); (ii) OCD symptoms severity did not increase, but the insight worsened (p = 0.028); (iii) the proportion of OCD patients showing hygiene-related symptoms increased (p = 0.031 for obsessions of contamination), whereas that of patients with checking-related symptoms decreased.

Conclusions
The lockdown-induced psychological distress apparently changed the characteristics and the pattern of OCD symptoms expression but not their overall severity. This evidence confirms the heterogeneity and changing nature of OCD symptoms, strongly depending on the environmental circumstances.
Disparities in Diagnosis, Treatment Access, and Time to Treatment Among Hispanic Men With Metastatic Prostate Cancer
Authors: Hougen Helen Y. , Swami Nishwant , Dee Edward Christopher , Alshalalfa Mohammed , Meiyappan Karthik , Florez Narjust , Penedo Frank J. , Nguyen Paul L. , Punnen Sanoj , Mahal Brandon A. 
Published: June 2023

PURPOSE Reporting racial/ethnic disparities in aggregate obscures within-group heterogeneity. We sought to identify disparities in diagnosis and treatment in Hispanic subpopulations with metastatic prostate cancer (mPCa). METHODS We disaggregated men with prostate adenocarcinoma from the National Cancer Database from 2004 to 2017 by racial subgroup and Hispanic background. We assessed (1) presenting with mPCa, (2) receiving any treatment, and (3) receiving delayed treatment beyond 90 days. Logistic regression and adjusted odds ratios (aOR) were reported. RESULTS Hispanic men had greater odds of presenting with mPCa (aOR, 1.54; 95% CI, 1.50 to 1.58; P < .001) compared with non-Hispanic White (NHW) men. All Hispanic racial subgroups were more likely to present with mPCa, with the highest risk in Hispanic Black (HB) men (aOR, 1.68; 95% CI, 1.46 to 1.93; P < .01). Men from all Hispanic backgrounds had higher odds of presenting with mPCa, especially Mexican men (aOR, 1.99; 95% CI, 1.86 to 2.12; P < .01). Hispanic men were less likely to receive any treatment (aOR, 0.60; 95% CI, 0.53 to 0.67; P < .001), and this effect was particularly strong for Hispanic White patients (aOR, 0.58; 95% CI, 0.52 to 0.66; P < .001) and Dominican men (aOR, 0.52; 95% CI, 0.28 to 0.98; P = .044). Hispanic men were more likely to experience treatment delays compared with NHW men (aOR, 1.38; 95% CI, 1.26 to 1.52; P < .001) and in particular HB (aOR, 1.83; 95% CI, 1.22 to 2.75; P = .002) and South/Central American men (aOR, 1.48; 95% CI, 1.07 to 2.04; P = .018). CONCLUSION Differences exist in stage at presentation, treatment receipt, and delays in treatment on disaggregation by racial subgroup and Hispanic heritage. We need to study the potential mechanisms of the observed variations to help develop targeted interventions.
Diurnal Range and Intra-patient Variability of ACTH Is Restored With Remission in Cushing's Disease
Authors: Alvarez Reinier , Hogan Elizabeth , Asuzu David T , Wu Tianxia , Oshegbo Gloria , McGlotten Raven , Cortes Michaela , Hayes Christina , Stratakis Constantine A , Tatsi Christina , Nieman Lynnette K , Chittiboina Prashant 
Published: June 2023

Abstract

Context
Single ACTH measurements have limited ability to distinguish patients with Cushing's disease (CD) from those in remission or with other conditions.

Objective
To investigate the changes in ACTH levels before and after transsphenoidal surgery (TSS) to identify trends that could confirm remission from CD and help establish ACTH cutoffs for targeted clinical trials in CD.

Design
Retrospective analysis of CD patients who underwent TSS from 2005 to -2019.

Setting
Referral center.

Patients
CD patients (n = 253) with ACTH measurements before and after TSS.

Interventions
TSS for CD.

Main Outcome Measures
Remission after TSS.

Results
Remission was observed in 223 patients after TSS. Those in remission had higher ACTH variability at AM (P = .02) and PM (P &lt; .001) time points compared to nonremission. The nonremission group had a significantly narrower diurnal range compared to the remission group (P = &lt;.0001). A decrease in plasma ACTH of ≥50% from mean preoperative levels predicted CD remission after TSS, especially when using PM values. The absolute plasma ACTH concentration and ratio of preoperative to postoperative values were significantly associated with nonremission after multivariable logistic regression (adj P &lt; .001 and .001, respectively).

Conclusions
Our findings suggest that ACTH variability is suppressed in CD, and remission from CD is associated with the restoration of this variability. Furthermore, a decrease in plasma ACTH by 50% or more may serve as a predictor of remission post-TSS. These insights could guide clinicians in developing rational outcome measures for interventions targeting CD adenomas.
Reevaluating the Role of Progesterone in Ovarian Cancer: Is Progesterone Always Protective?
Authors: Mauro Laura J , Spartz Angela , Austin Julia R , Lange Carol A 
Published: June 2023

Abstract
Ovarian cancer (OC) represents a collection of rare but lethal gynecologic cancers where the difficulty of early detection due to an often-subtle range of abdominal symptoms contributes to high fatality rates. With the exception of BRCA1/2 mutation carriers, OC most often manifests as a post-menopausal disease, a time in which the ovaries regress and circulating reproductive hormones diminish. Progesterone is thought to be a “protective” hormone that counters the proliferative actions of estrogen, as can be observed in the uterus or breast. Like other steroid hormone receptor family members, the transcriptional activity of the nuclear progesterone receptor (nPR) may be ligand dependent or independent and is fully integrated with other ubiquitous cell signaling pathways often altered in cancers. Emerging evidence in OC models challenges the singular protective role of progesterone/nPR. Herein, we integrate the historical perspective of progesterone on OC development and progression with exciting new research findings and critical interpretations to help paint a broader picture of the role of progesterone and nPR signaling in OC. We hope to alleviate some of the controversy around the role of progesterone and give insight into the importance of nPR actions in disease progression. A new perspective on the role of progesterone and nPR signaling integration will raise awareness to the complexity of nPRs and nPR-driven gene regulation in OC, help to reveal novel biomarkers, and lend critical knowledge for the development of better therapeutic strategies.
Loss of flrt2 gene leads to microphthalmia in zebrafish
Authors: Yang Siyu , Huang Lianggui , Liang Huiling , Guo Jingyi , Liu Liyue , Chen Shuyi , Cao Mingzhe 
Published: June 2023

ABSTRACT
As a member of the fibronectin leucine-rich transmembrane (flrt) gene family, fibronectin leucine-rich transmembrane 2 (flrt2) is strongly expressed in a subset of sclerotome cells, and the resultant protein interacts with FGFR1 in the FGF signaling pathway during development. Studies on flrt2 have focused mainly on its roles in the brain, heart and chondrogenesis. However, reports on its expression and function in the zebrafish retina are lacking. Here, we detected the high expression of flrt2 in zebrafish retina using in situ hybridization technique and developed an flrt2-knockout (KO) zebrafish line using CRISPR/Cas9 genome editing. Quantitative real-time PCR was used to measure the expression levels of flrt2, which results in an approximately 60% mRNA reduction. The flrt2-KO zebrafish eyes’ altered morphological, cellular, and molecular events were identified using BrdU labeling, TUNEL assay, immunofluorescent staining, fluorescent dye injection and RNA sequencing. Abnormal eye development, known as microphthalmia, was found in flrt2-KO larvae, and the retinal progenitor cells exhibited increased apoptosis, perhaps owing to the combined effects of crx, neurod4, atoh7, and pcdh8 downregulation and Casp3a and Caspbl upregulation. In contrast, the retinal neural development, as well as retinal progenitor cell differentiation and proliferation, were not affected by the flrt2 deletion. Thus, flrt2 appears to play important roles in retinal development and function, which may provide the basis for further investigations into the molecular mechanisms of retinal development and evolution.
Immature human engineered heart tissues engraft in a guinea pig chronic injury model
Authors: von Bibra Constantin , Shibamiya Aya , Bähr Andrea , Geertz Birgit , Köhne Maria , Stuedemann Tim , Starbatty Jutta , Horneffer-van der Sluis Verena , Klostermeier Ulrich C. , Hornaschewitz Nadja , Li Xinghai , Wolf Eckhard , Klymiuk Nikolai , Krane Markus , Kupatt Christian , Hiebl Bernhard , Eschenhagen Thomas , Weinberger Florian 
Published: June 2023

ABSTRACT
Engineered heart tissue (EHT) transplantation represents an innovative, regenerative approach for heart failure patients. Late preclinical trials are underway, and a first clinical trial started recently. Preceding studies revealed functional recovery after implantation of in vitro-matured EHT in the subacute stage, whereas transplantation in a chronic injury setting was less efficient. When transplanting matured EHTs, we noticed that cardiomyocytes undergo a dedifferentiation step before eventually forming structured grafts. Therefore, we wanted to evaluate whether immature EHT (EHTIm) patches can be used for transplantation. Chronic myocardial injury was induced in a guinea pig model. EHTIm (15×106 cells) were transplanted within hours after casting. Cryo-injury led to large transmural scars amounting to 26% of the left ventricle. Grafts remuscularized 9% of the scar area on average. Echocardiographic analysis showed some evidence of improvement of left-ventricular function after EHTIm transplantation. In a small translational proof-of-concept study, human scale EHTIm patches (4.5×108 cells) were epicardially implanted on healthy pig hearts (n=2). In summary, we provide evidence that transplantation of EHTIm patches, i.e. without precultivation, is feasible, with similar engraftment results to those obtained using matured EHT.
NR2F1 shapes mitochondria in the mouse brain, providing new insights into Bosch-Boonstra-Schaaf optic atrophy syndrome
Authors: Bonzano Sara , Dallorto Eleonora , Molineris Ivan , Michelon Filippo , Crisci Isabella , Gambarotta Giovanna , Neri Francesco , Oliviero Salvatore , Beckervordersandforth Ruth , Lie Dieter Chichung , Peretto Paolo , Bovetti Serena , Studer Michèle , Marchis Silvia De 
Published: June 2023

ABSTRACT
The nuclear receptor NR2F1 acts as a strong transcriptional regulator in embryonic and postnatal neural cells. In humans, mutations in the NR2F1 gene cause Bosch-Boonstra-Schaaf optic atrophy syndrome (BBSOAS), a rare neurodevelopmental disorder characterized by multiple clinical features including vision impairment, intellectual disability and autistic traits. In this study, we identified, by genome-wide and in silico analyses, a set of nuclear-encoded mitochondrial genes as potential genomic targets under direct NR2F1 transcriptional control in neurons. By combining mouse genetic, neuroanatomical and imaging approaches, we demonstrated that conditional NR2F1 loss of function within the adult mouse hippocampal neurogenic niche results in a reduced mitochondrial mass associated with mitochondrial fragmentation and downregulation of key mitochondrial proteins in newborn neurons, the genesis, survival and functional integration of which are impaired. Importantly, we also found dysregulation of several nuclear-encoded mitochondrial genes and downregulation of key mitochondrial proteins in the brain of Nr2f1-heterozygous mice, a validated BBSOAS model. Our data point to an active role for NR2F1 in the mitochondrial gene expression regulatory network in neurons and support the involvement of mitochondrial dysfunction in BBSOAS pathogenesis.
Fertility-Sparing Treatment for Early-Stage Cervical Cancer ≥ 2 cm: Can One Still Effectively Become a Mother? A Systematic Review of Fertility Outcomes
Authors: Ronsini Carlo , Solazzo M. C. , Molitierno R. , De Franciscis P. , Pasanisi F. , Cobellis L. , Colacurci N. 
Published: June 2023

Abstract
Background
Fertility-sparing treatments (FSTs) have played a crucial role in the management of early-stage cervical cancer (ECC); however, there is currently no standard of care for women with ECC ≥ 2 cm who wish to preserve their fertility. The current orientation of the scientific community comprises upfront surgical techniques and neoadjuvant chemotherapy (NACT) followed by minor surgery such us conization. However these approaches are not standardized. This systematic review aimed to collect the evidence in the literature regarding the obstetric outcomes of the different techniques for applying FSTs in ECC ≥ 2 cm.

Methods
A systematic review was performed in September 2022 using the Pubmed and Scopus databases, from the date of the first publication. We included all studies containing data regarding pregnancy, birth, and preterm rates.

Results
Fifteen studies fulfilled the inclusion criteria, and 352 patients were analyzed regarding fertility outcomes. Surgery-based FST showed the pregnancy rate (22%), birth rate (11%), and preterm rate (10%). Papers regarding FST using the NACT approach showed a pregnancy rate of 44%, with a birth rate of 45% in patients who managed to get pregnant. The preterm rate amounted to 44%, and pregnancy rates and birth rates were significantly different between the two groups (p < 0.001).

Conclusion
Fertility preservation in patients with ECC > 2 cm is challenging. The endpoint for evaluating the best treatment should include oncological and fertility outcomes together. From this prospective, NACT followed by less radical surgery could be a reasonable compromise.
Exogenous Ketosis Improves Sleep Efficiency and Counteracts the Decline in REM Sleep after Strenuous Exercise
Authors: ROBBERECHTS RUBEN , ALBOUY GENEVIÈVE , HESPEL PETER , POFFÉ CHIEL 
Published: June 2023

ABSTRACT

Introduction
Available evidence indicates that ketone bodies may improve sleep quality. Therefore, we determined whether ketone ester (KE) intake could counteract sleep disruptions induced by strenuous exercise.

Methods
Ten well-trained cyclists with good sleep quality participated in a randomized crossover design consisting of two experimental sessions each involving a morning endurance training and an evening high-intensity interval training ending 1 h before sleep, after which polysomnography was performed overnight. Postexercise and 30 min before sleeping time, subjects received either 25 g of KE (EXKE) or a placebo drink (EXCON). A third session without exercise but with placebo supplements (RCON) was added to evaluate the effect of exercise per se on sleep.

Results
Blood d-β-hydroxybutyrate concentrations transiently increased to ~3 mM postexercise and during the first part of the night in EXKE but not in EXCON or RCON. Exercise significantly reduced rapid eye movement sleep by 26% (P = 0.001 vs RCON) and increased wakefulness after sleep onset by 95% (P = 0.004 vs RCON). Interestingly, KE improved sleep efficiency by 3% (P = 0.040 vs EXCON) and counteracted the exercise-induced decrease in rapid eye movement sleep (P = 0.011 vs EXCON) and the increase in wakefulness after sleep onset (P = 0.009 vs EXCON). This was accompanied by a KE-induced increase in dopamine excretion (P = 0.033 vs EXCON), which plays a pivotal role in sleep regulation. In addition, exercise increased sleep spindle density by 36% (P = 0.005 vs RCON), suggesting an effect on neural plasticity processes during sleep.

Conclusions
These data indicate that KE ingestion improves sleep efficiency and quality after high-intensity exercise. We provide preliminary evidence that this might result from KE-induced increases in dopamine signaling.
Development of Cycling Performance Variables and Durability in Female and Male National Team Cyclists: From Junior to Senior
Authors: ALMQUIST NICKI WINFIELD , HANSEN JOAR , RØNNESTAD BENT R. 
Published: June 2023

ABSTRACT

Aim
This study investigated the development of power profiles and performance-related measures from the junior level (<19 yr) via U23 (19–23 yr) to senior level (>23 yr) in 19 female and 100 male Norwegian national team cyclists.

Methods
A total of 285 tests were performed in a 3-d laboratory-standardized testing regime. The tests included power profiles with shorter duration (6–60 s) and longer durations (12–30 min) together with performance-related measures: critical power (CP), work capacity above CP (W′), power output at 4 and 2 mmol·L−1 [BLa−] (L4 and L2), maximal aerobic power (Wmax), and maximal oxygen uptake (V̇O2max), gross efficiency (GE), and pedaling efficiency.

Results
Females and males evolve similarly when maturing from junior via U23 to senior categories (all P > 0.07), except for V̇O2max, which increased in females (but not males) from junior to senior level (534 ± 436 mL·min−1, P = 0.013). In general, only performances of longer durations improved with age (12 and 30 min, P = 0.028 and P = 0.042, respectively). Performance-related measures like Wmax, V̇O2max, CP, L4, L2, and pedaling efficiency in the fresh state improved with age (all P ≤ 0.025). Importantly, performance in the semifatigued state during a 5-min maximal test was also improved with age (P = 0.045) despite a higher external energy expenditure before the test (P = 0.026).

Conclusions
Junior cyclists show highly developed sprint abilities, and the primary improvements of absolute power outputs and performance-related measures are seen for durations >60 s when maturing to U23 and senior categories. However, the durability, i.e., the capacity to maintain performance in a semifatigued state, is improved with age.
A qualitative study of patients' experiences of living with hard-to-heal leg ulcers
Authors: Olsson Malin , Wadin Lisa , Åhlén Jenny , Friman Anne 
Published: June 2023

Background: Patients with hard-to-heal leg ulcers are often older and have underlying conditions that contribute to making wound healing more difficult. Hard-to-heal leg ulcers are often treated in primary care and form a large part of the district nurse's work. Aim: To describe patients' experiences of living with hard-to-heal leg ulcers. Methods: This qualitative study undertook 18 interviews with patients in primary care with hard-to-heal leg ulcers. Findings: A total of three categories were identified: ‘Living with changes in everyday life’, ‘Being dependent on care’, and ‘Experiencing and dealing with suffering’. The patients described limitations in physical activity and changes in social interaction. Suffering was described in different ways and also resulted in coping strategies. Conclusions: Living with hard-to-heal leg ulcers affects the patient's everyday life physically and mentally. Knowledge about the complexity of patients' experiences can contribute to better care and increased quality of life in a difficult situation.
High rate of radiolucent lines following the cemented original design of the ATTUNE total knee arthroplasty
Authors: Prodromidis Apostolos D. , Chloros George D. , Thivaios Georgios C. , Sutton Paul M. , Pandit Hemant , Giannoudis Peter V. , Charalambous Charalambos P. 
Published: June 2023

AimsLoosening of components after total knee arthroplasty (TKA) can be associated with the development of radiolucent lines (RLLs). The aim of this study was to assess the rate of formation of RLLs in the cemented original design of the ATTUNE TKA and their relationship to loosening.MethodsA systematic search was undertaken using the Cochrane methodology in three online databases: MEDLINE, Embase, and CINAHL. Studies were screened against predetermined criteria, and data were extracted. Available National Joint Registries in the Network of Orthopaedic Registries of Europe were also screened. A random effects model meta-analysis was undertaken.ResultsOf 263 studies, 12 were included with a total of 3,861 TKAs. Meta-analysis of ten studies showed high rates of overall tibial or femoral RLLs for the cemented original design of the ATTUNE TKA. The overall rate was 21.4% (95% confidence interval (CI) 12.7% to 33.7%) for all types of design but was higher for certain subgroups: 27.4% (95% CI 13.4% to 47.9%) for the cruciate-retaining type, and 29.9% (95% CI 15.6% to 49.6%) for the fixed-bearing type. Meta-analysis of five studies comparing the ATTUNE TKA with other implants showed a significantly higher risk of overall tibial or femoral RLLs (odds ratio (OR) 2.841 (95% CI 1.219 to 6.623); p = 0.016) for the ATTUNE. The rates of loosening or revision for loosening were lower, at 1.2% and 0.9% respectively, but the rates varied from 0% to 16.3%. The registry data did not report specifically on the original ATTUNE TKA or on revision due to loosening, but ‘all-cause’ five-year revision rates for the cemented ATTUNE varied from 2.6% to 5.9%.ConclusionThe original cemented ATTUNE TKA has high rates of RLLs, but their clinical significance is uncertain given the overall low associated rates of loosening and revision. However, in view of the high rates of RLLs and the variation in the rates of loosening and revision between studies and registries, close surveillance of patients who have undergone TKA with the original ATTUNE system is recommended.Cite this article: Bone Joint J 2023;105-B(6):610–621.