bluuebunny/crossref_metadata_2025_split huggingface dataset:
PRL-R Variants Are Not Only Associated With Prolactinomas But Also With Dopamine Agonist Resistance
Authors: de Castro Moreira Andrea Ramos , Trarbach Ericka , Bueno Cristina Bellotti Formiga , Monteiro Anna Louise Stellfeld , Grande Isabella Pacetti Pajaro , Padula Mario , Maciel Gustavo Arantes Rosa , Glezer Andrea 
Published: January 2023

Abstract

Context
Knockout prolactin receptor gene (PRL-R) mice are animal models for prolactinomas and PRL acts via autocrine/paracrine inhibiting lactotroph proliferation. Recently, variants of the PRL-R were identified in prolactinoma patients and their frequency was higher compared to individuals from the genomic database.

Objective
We analyzed PRL-R variants frequency in an extensive cohort of prolactinoma patients and evaluated their association with clinical, laboratorial, and imaging characteristics and hormonal response to cabergoline.

Design
Observational, retrospective, and cross-sectional study.

Setting
This study took place at the Neuroendocrinology Unit of Clinics Hospital, Medical School of University of São Paulo, Brazil, a tertiary referral center.

Patients and Methods
Study participants included adults with sporadic prolactinomas treated with cabergoline, where response to therapy was defined by prolactin normalization with up to 3 mg/week doses. DNA was extracted from blood samples and the PRL-R was analyzed by polymerase chain reaction techniques and automatic sequencing. The association of PRL-R variants with serum prolactin levels, maximal tumor diameter, tumor parasellar invasiveness, and response to cabergoline was analyzed.

Results
We found 6 PRL-R variants: p.Ile100(76)Val, p.Ile170(146)Leu, p.Glu400(376)Gln/p.Asn516(492)Ile, p.Glu470Asp e p.Ala591Pro; the last 2 are newly described in prolactinomas’ patients. The variants p.Glu400(376)Gln/p.Asn516(492)Ile and p.Ala591Pro were more frequent amongst patients compared to genomic databases, and the p.Asn516(492)Ile showed pathogenic potential using in silico analysis as previously described. PRL-R variants were associated with male sex (P = 0.015), higher serum PRL levels (P = 0.007), larger tumors (P = 0.001), and cabergoline resistance (P &lt; 0.001).

Conclusions
The prolactin/prolactin receptor system seems to be related to prolactinoma tumorigenesis and cabergoline resistance. Additional studies are needed to better understand the PRL-R variants’ role and their potential as therapeutic targets.
Consequences of General Anesthesia in Infancy on Behavior and Brain Structure
Authors: Salaün Jean-Philippe , Chagnot Audrey , Cachia Arnaud , Poirel Nicolas , Datin-Dorrière Valérie , Dujarrier Cléo , Lemarchand Eloïse , Rolland Marine , Delalande Lisa , Gressens Pierre , Guillois Bernard , Houdé Olivier , Levard Damien , Gakuba Clément , Moyon Marine , Naveau Mikael , Orliac François , Orliaguet Gilles , Hanouz Jean-Luc , Agin Véronique , Borst Grégoire , Vivien Denis 
Published: January 2023

BACKGROUND:
One in 7 children will need general anesthesia (GA) before the age of 3. Brain toxicity of anesthetics is controversial. Our objective was to clarify whether exposure of GA to the developing brain could lead to lasting behavioral and structural brain changes.

METHODS:
A first study was performed in mice. The behaviors (fear conditioning, Y-maze, and actimetry) and brain anatomy (high-resolution magnetic resonance imaging) of 6- to 8-week-old Swiss mice exposed or not exposed to GA from 4 to 10 days old were evaluated. A second study was a complementary analysis from the preexisting APprentissages EXécutifs et cerveau chez les enfants d’âge scolaire (APEX) cohort to assess the replicability of our data in humans. The behaviors (behavior rating inventory of executive function, emotional control, and working memory score, Backward Digit Span, and Raven 36) and brain anatomy (high-resolution magnetic resonance imaging) were compared in 102 children 9 to 10 years of age exposed or not exposed to a single GA (surgery) during infancy.

RESULTS:
The animal study revealed chronic exacerbated fear behavior in the adult mice (95% confidence interval [CI], 4–80; P = .03) exposed to postnatal GA; this was associated with an 11% (95% CI, 7.5–14.5) reduction of the periaqueductal gray matter (P = .046). The study in humans suggested lower emotional control (95% CI, 0.33–9.10; P = .06) and a 6.1% (95% CI, 4.3–7.8) reduction in the posterior part of the right inferior frontal gyrus (P = .019) in the children who had been exposed to a single GA procedure.

CONCLUSIONS:
The preclinical and clinical findings of these independent studies suggest lasting effects of early life exposure to anesthetics on later emotional control behaviors and brain structures.
A Protocol for Reducing Intensive Care Utilization After Craniotomy: A 3-Year Assessment
Authors: Ruiz Colón Gabriela D. , Ohkuma Rika , Pendharkar Arjun V. , Heifets Boris D. , Li Gordon , Lu Amy , Gephart Melanie Hayden , Ratliff John K. 
Published: January 2023

BACKGROUND:
Craniotomy patients have traditionally received intensive care unit (ICU) care postoperatively. Our institution developed the “Non-Intensive CarE” (NICE) protocol to identify craniotomy patients who did not require postoperative ICU care.

OBJECTIVE:
To determine the longitudinal impact of the NICE protocol on postoperative length of stay (LOS), ICU utilization, readmissions, and complications.

METHODS:
In this retrospective cohort study, our institution's electronic medical record was queried to identify craniotomies before protocol deployment (May 2014-May 2018) and after deployment (May 2018-December 2021). The primary end points were average postoperative LOS and ICU utilization; secondary end points included readmissions, reoperation, and postoperative complications rate. End points were compared between pre- and postintervention cohorts.

RESULTS:
Four thousand eight hundred thirty-seven craniotomies were performed from May 2014 to December 2021 (2302 preprotocol and 2535 postprotocol). Twenty-one percent of postprotocol craniotomies were enrolled in the NICE protocol. After protocol deployment, the overall postoperative LOS decreased from 4.0 to 3.5 days (P = .0031), which was driven by deceased postoperative LOS among protocol patients (average 2.4 days). ICU utilization decreased from 57% of patients to 42% (P < .0001), generating ∼$760 000 in savings. Return to the ICU and complications decreased after protocol deployment. 5.8% of protocol patients had a readmission within 30 days; none could have been prevented through ICU stay.

CONCLUSION:
The NICE protocol is an effective, sustainable method to increase ICU bed availability and decrease costs without changing outcomes. To our knowledge, this study features the largest series of patients enrolling in an ICU utilization reduction protocol. Careful patient selection is a requirement for the success of this approach.
MAAS-MOBILITY AS A SERVICE. DEVELOPMENT PROSPECTS
Authors: Nadiryan Sofiya L. , Kotenkova Irina N. 
Published: January 2023

In this article, the authors consider the main provisions of the MaaS concept – mobility as a service. This is a type of service that, through a shared digital channel, allows users to plan, book and pay for various types of mobility services.
Purpose – the conditions for the introduction and implementation of the MaaS concept in modern cities are analyzed.
Methodology: the article used statistical analysis, synthesis.
Results: the factors that increase the effectiveness of the proposed concept and the possibility of its implementation in specific conditions are identified.
Practical implications: research activity on the development of new approaches in the field of organization of transportation and transport services.
Cannabis and Sleep: A Systematic Review of the Effects of Cannabinoids on Sleep Disorders
Authors: Luchowska Anna , Sroczyńska Monika , Żaczek Aleksandra 
Published: January 2023

Introduction: Sleep disorders are a common problem in society in the modern world. Patients are increasingly seeking alternative treatments for insomnia in order to reduce the side effects of prescription drugs. A new trend is the use of cannabinoids contained in cannabis plants to treat sleep disorders, making patients looking for a solution to their problem more and more eager.Aim of the study: The purpose of this paper is to present contemporary knowledge of the therapeutic benefits of cannabis compounds in treating sleep disorders and improving sleep parameters. Materials and methods: The National Center for Biotechnology Information/PubMed and Google Scholar medical databases were comprehensively analyzed by entering the keywords: cannabis, sleep disorders, insomnia, cannabinoids, THC, CBD in their respective configurations. Analyzing the searched literature, data from 18 scientific articles from the last five years (2017-2022) were evaluated.Results: Cannabinoids may have benefits in sleep-related disorders. The literature does not agree on the effectiveness of their use in treating sleep disorders. The highly variable availability of cannabinoid formulations on the market makes it difficult to develop appropriate dosages for the treatment of insomnia.Conclusions: Research on cannabis and sleep is in its early stages and needs to be continued in order to improve knowledge. There is a need for further long-term studies that are rigorously controlled and use larger study groups.
Synthetic sweeteners and their impact on the gut microbiota - current state of knowledge
Authors: Wąsik Karolina , Tomaszuk Sebastian , Wojtuś Magda 
Published: January 2023

Introduction and purpose:
The aim of artificial sweeteners is to replace the sweetness of sugar without contributing to the higher energy consumption or unfavorable metabolic effects conventional sugar causes. Synthetic sweeteners - one of the most popular groups - are labeled as safe for use in foods and represented by acesulfame K, aspartame, neotame, saccharin, sucralose, cyclamate and advantame. Although they underwent safety procedures, their possible unbeneficial effects are still being evaluated. In this paper we focus on their impact on the gut microbiome.
Brief description of the state of knowledge:
For now, the advantage of search conducted on animals is observed. Those papers show the possibility of a relationship between artificial sweeteners and composition of the gut microbiota. Changes that were observed affected the gut microbiota in a negative way as they may be responsible for causing disbalance in the conglomerate of microorganisms.
Studies on humans are limited. Long term consumption of acesulfame K and sucralose is linked with modulation of the composition of the microbiota. It has also been shown that synthetic sweeteners are able to increase the ability of bacteria to form a biofilm.
Conclusions:
Heretofore published paperworks about the impact of synthetic sweeteners on the gut microbiota are not sufficient to conduct valuable and unambiguous conclusions. Evidence collected until now is leading to a deduction that gut microbiota can be affected by the consumption of the sugar surrogates although more data is needed to clearly determine their possible role.
Infertile men with semen parameters above WHO reference limits at first assessment may deserve a second semen analysis: Challenging the guidelines in the real-life scenario
Authors: Boeri Luca , Pozzi Edoardo , Capogrosso Paolo , Fallara Giuseppe , Belladelli Federico , Candela Luigi , Schifano Nicolò , Corsini Christian , Cazzaniga Walter , Cignoli Daniele , Ventimiglia Eugenio , Pontillo Marina , Alfano Massimo , Montorsi Francesco , Salonia Andrea 
Published: January 2023

Objectives
To investigate which infertile men with semen parameters above WHO reference limits at first semen analysis deserve a second semen test.

Materials and methods
Data from 1358 consecutive infertile men were analysed. Patients underwent two consecutive semen analyses at the same laboratory. Descriptive statistics and logistic regression models tested the association between clinical variables and semen parameters. A new predicting model was identified through logistic regression analysis exploring potential predictors of semen parameters below WHO reference limits after a previously normal one. Diagnostic accuracy of the new model was compared with AUA/ASRM and EAU guidelines. Decision curve analyses (DCA) tested their clinical benefit.

Results
Of 1358, 212 (15.6%) infertile men had semen parameters above WHO reference limits at first analysis. Of 212, 87 (41.0%) had a second semen analysis with results above WHO reference limits. Men with sperm parameters below reference limits at second analysis had higher FSH values, but lower testicular volume (TV) (all p<0.01) compared to men with a second semen analysis above WHO limits. At multivariable logistic regression analysis, lower TV (OR 0.9, p = 0.03), higher FSH (OR 1.2, p<0.01), and lower total sperm count (OR 0.9, p<0.01) were associated with second semen analyses below WHO limits. DCA showed the superior net benefit of using the new model, compared to both AUA/ASRM and EAU guidelines to identify those men with a second semen sample below WHO limits after a previously normal one.

Conclusions
Approximately 60% of infertile men with a first semen analysis above WHO limits have a second analysis with results below limits. The newly identified risk model might be useful to select infertile men with initial semen results above WHO limits who deserve a second semen analysis.
PL Morse theory in low dimensions
Authors: Grunert Romain , Kühnel Wolfgang , Rote Günter 
Published: January 2023

Abstract
We discuss a PL analog of Morse theory for PL manifolds. There are several notions of regular and critical points. A point is homologically regular if the homology does not change when passing through its level; it is strongly regular if the function can serve as one coordinate in a chart. Several criteria for strong regularity are presented. In particular, we show that in dimensions d ≤ 4 a homologically regular point on a PL d-manifold is always strongly regular. Examples show that this fails in higher dimensions d ≥ 5. One of our constructions involves an embedding of the dunce hat into 4-space and Mazur’s contractible 4-manifold. Finally, decidability questions in this context are discussed.
Determination of parathyroid hormone: from radioimmunoassay to LCMS/MS
Authors: Cavalier Etienne 
Published: January 2023

Abstract
Parathyroid hormone (PTH) determination is of paramount importance for the exploration of diseases related with calcium metabolism and for the follow-up of patients suffering from bone and mineral disorders associated with chronic kidney diseases (CKD-MBD). Unfortunately, the biologically active form of PTH, i.e. 1–84 PTH, circulates in the blood stream with many fragments and post-translationally modified forms, which decreases the specificity of immunoassays. The assays used to measure PTH, either from 2nd or 3rd generation, are not standardised, which may lead to interpretation errors and clinical consequences. Reference ranges for PTH have neither been always correctly established and the stability of the peptide is also a matter of concern. Fortunately, these last years, newer techniques using mass spectrometry (either high resolution or triple quadripole) coupled with liquid chromatography have been developed, which will help to standardise the different assays. Indeed, PTH assays standardisation is one of the task of the IFCC Committee for Bone Metabolism. Such standardisation will allow a better consistency in the interpretation of the results and will promote studies aiming at the establishment of correct reference ranges.
LMS-based continuous reference percentiles for 14 laboratory parameters in the CALIPER cohort of healthy children and adolescents
Authors: Wilson Siobhan M. , Bohn Mary Kathryn , Madsen Andre , Hundhausen Thomas , Adeli Khosrow 
Published: January 2023

Abstract

Objectives
Marked physiological changes in growth and development present challenges in defining pediatric reference intervals for biomarkers of health and disease. Lambda, Mu, and Sigma (LMS)-based statistical modeling provides a continuous normal distribution by negating skewness and variation, and is commonly used to establish growth charts. Such LMS reference curves are suggested to enhance laboratory test result interpretation. The current study establishes LMS-based continuous reference percentiles for 14 biomarkers in the CALIPER cohort of healthy children and adolescents.

Methods
Data from healthy children and adolescents aged 1–<19 years were used to establish continuous reference percentiles using a novel LMS-based statistical method, including 2.5th, 25th, 50th, 75th, and 97.5th percentiles. The LMS approach applies a Box-Cox data transformation and summarizes continuous distributions by age via three curves: skewness (Lambda), median (Mu), and coefficient of variation (Sigma).

Results
LMS-based percentiles and z-scores were generated for 14 common pediatric biomarkers that demonstrate dynamic concentration patterns with age (e.g., alkaline phosphatase) and/or wherein the magnitude of difference from the population mean may be clinically relevant (e.g., triglycerides). The LMS model captured age- and sex-specific distributions accurately and was not substantially influenced by outlying points.

Conclusions
This is the first study to establish LMS-based continuous reference percentiles for biochemical markers in a healthy Canadian pediatric population. The current LMS-based approach builds upon previous continuous reference interval models by providing graded percentiles to improve test result interpretation, particularly with repeated measures over time. This method may assist in facilitating a patient-centered approach to laboratory medicine.
Social Connection when Physically Isolated: Family Experiences in Using Video Calls
Authors: Kacane Ilze , Hernández-Serrano Maria Jose 
Published: January 2023

Abstract
Digital (video) calls have become a significant tool during the challenging times marked by the COVID-19 pandemic. The article focuses on the perceived functionality of video calls for maintaining social contacts and overcoming loneliness in celebrating family festivities limited by physical distance policies. The qualitative study conducted at the end of 2021 in Latvia and Spain examines families’ cultural socialisation via digital tools and, based on data obtained from semi-structured in-depth interviews, assesses the users’ digital experiences in celebrating Christmas and the New Year from retrospective and prospective standpoints. The obtained data revealed that although digital interactions were acknowledged as an alternative means for ensuring togetherness, preserving and facilitating emotional connection, and experiencing a feeling of belonging and shared identity, they were perceived as the context of exception. The findings complement existing studies that the pandemic contributed to bridging the digital gap among generations with coordinated and negotiated conceptions of the functionality of digital tools. Video calls ensured a sense of social and emotional connectedness and inspired the appearance of virtual celebration ideas.
Spin–orbit coupling induced by ascorbic acid crystals
Authors: Grenapin Florence , D’Errico Alessio , Karimi Ebrahim 
Published: January 2023

Abstract
Some anisotropic materials form semicrystalline structures, called spherulites, when observed in a polarisation microscope, exhibit a characteristic “maltese-cross”-like pattern. While this observation has been hitherto considered as a tool to characterize these materials, we show that these patterns are associated with a strong light’s spin–orbit coupling induced by the spherulite structures. We experimentally demonstrate these effects using samples of crystallized ascorbic acid and observing the creation of optical vortices in transmitted laser beams, as well as the formation of inhomogeneous polarisation patterns. Our findings suggest the use of some spherulites based on other materials in frequency ranges, e.g. in the THz domain, where polarisation and spatial shaping of electromagnetic radiation is still a challenging task.
Purcell enhancement and polarization control of single-photon emitters in monolayer WSe2 using dielectric nanoantennas
Authors: Azzam Shaimaa I. , Parto Kamyar , Moody Galan 
Published: January 2023

Abstract
Two-dimensional (2D) materials have shown great promise as hosts for high-purity deterministic single-photon sources. In the last few years, the underlying physics of single photon emission in 2D materials have been uncovered, and their optical properties have been improved to meet criteria for a variety of quantum technologies and applications. In this work, we take advantage of the unique characteristics of dielectric nanoantennas in manipulating the electromagnetic response on a sub-wavelength scale to localize and control defect-based single-photon emitters (SPEs) in 2D layered materials. We show that dielectric nanoantennas are capable of inducing high Purcell enhancement >20 and therefore brighter single-photon emission, which is characterized by a reduction of the emitters’ radiative lifetimes and enhancement of their brightness by more than an order of magnitude. We demonstrate that the sub-wavelength-scale dielectric nanoantennas can be designed to also impose a predetermined strain profile that determines the confinement potential of the SPE, leading to robust control over the optical polarization with up to 94% extinction ratio. The combination of large Purcell enhancement, polarization orientation, and site control through strain engineering demonstrates the advantages and unique capabilities of dielectric nanoantennas for enhancing the quantum optical properties of 2D SPEs for quantum information technologies.
Three-dimensionally reconfigurable focusing of laser by mechanically tunable metalens doublet with built-in holograms for alignment
Authors: Jung Joonkyo , Kim Hyeonhee , Shin Jonghwa 
Published: January 2023

Abstract
Metalenses have potential to replace various bulky conventional optical elements with ultrathin nanostructure arrays. In particular, active metalenses with reconfigurable focusing capability have attracted considerable interest from the academic and industrial communities. However, their tuning range is currently restricted by limited material properties and fabrication difficulties. Here, a hybrid optical system capable of three-dimensional relocation of a focal spot is proposed and experimentally demonstrated. The system comprises a mechanically actuated passive metalens doublet that can be easily fabricated with commonly available materials and processes. An incident laser can be focused to a desired point in three-dimensional space simply by rotating two metalenses or changing their separation. In addition, exploiting the polarization-multiplexing capability of metasurfaces, a hologram is incorporated to the metalenses to guide rotational and positional alignment of two metasurfaces. The ease of fabrication and alignment provided by this approach could widen its application to many practical fields.