bluuebunny/crossref_metadata_2025_split huggingface dataset:
The side effects of dopamine receptor agonist drugs in Chinese prolactinoma patients: a cross sectional study
Authors: Ke Xiaoan , Wang Linjie , Chen Meiping , Liu Shanshan , Yu Na , Duan Lian , Gong Fengying , Zhu Huijuan 
Published: April 2022

Abstract
Background
Recently, side effects from Dopamine Receptor Agonist Drugs (DAs) in treating pituitary prolactinoma have raised widespread concern. This study explores the incidence and influencing factors of DAs-related side effects in Chinese prolactinoma patients.

Methods
A cross-sectional study was conducted. 51 prolactinoma patients treated with DAs, 12 prolactinoma or pituitary microadenoma patients without DAs treatment, and 33 healthy controls were included. The Barratt impulsivity scale-11, Patient Health Questionnaire 9, and the ICD screening questionnaire were all used to evaluate the psychological and physical side effects of DAs. Clinical data of all subjects were collected from their electronic medical records.

Results
The incidence of ICDs in the treated group, the untreated group, and control group was 9.8% (5/51), 16.7% (2/12), and 9.1% (3/33), respectively. In the treated group in particular, there were 1 patient (2%, 1/51), 2 patients (3.9%, 2/51), and 2 patients (3.9%, 2/51) with positive screening for punding, compulsive shopping, and hypersexuality, respectively. In terms of depression, the incidence of "minimal", "mild" and "moderate" depression in the treated group was 62.8% (32/51), 25.5% (13/51), and 5.9% (3/51), respectively. The incidence of physical symptoms was 51.0% (26/51) in the treated group and gastrointestinal symptoms were the most common symptoms (33.3%, 17/51). In addition, we found that the various parameters of DAs treatment had no association with the occurrence of physical symptoms or ICDs (all P > 0.05).

Conclusions
Chinese prolactinoma patients treated with DAs had a lower incidence of ICDs (9.8%), while gastrointestinal symptoms were common. In this way, more attention should be paid to side effects, especially physical symptoms, in Chinese prolactinoma patients with DAs therapy during follow-up regardless of dose.
Clinical and genetic analysis of pseudohypoparathyroidism complicated by hypokalemia: a case report and review of the literature
Authors: Huang Shaohan , He Yingzi , Lin Xihua , Sun Shuiya , Zheng Fenping 
Published: April 2022

Abstract
Background
Pseudohypoparathyroidism (PHP) encompasses a highly heterogenous group of disorders, characterized by parathyroid hormone (PTH) resistance caused by mutations in the GNAS gene or other upstream targets. Here, we investigate the characteristics of a female patient diagnosed with PHP complicated with hypokalemia, and her family members.

Case presentation and gene analysis
A 27-year-old female patient occasionally exhibited asymptomatic hypocalcemia and hypokalemia during her pregnancy 1 year ago. Seven months after delivery, she experienced tetany and dysphonia with diarrhea. Tetany symptoms were relieved after intravenous calcium gluconate supplementation and she was then transferred to our Hospital. Laboratory assessments of the patient revealed hypokalemia, hypocalcemia and hyperphosphatemia despite elevated PTH levels. CT scanning of the brain revealed globus pallidus calcification. Possible mutations in GNAS and hypokalemia related genes were identified using WES, exon copies of STX16 were analized by MLPA and the methylation status of GNAS in three differential methylated regions (DMRs) was analyzed by methylation-specific polymerase chain reaction, followed by confirmation with gene sequencing. The patient was clinically diagnosed with PHP-1b. Loss of methylation in the A/B region and hypermethylation in the NESP55 region were detected. No other mutations in GNAS or hypokalemia related genes and no deletions of STX16 exons were detected. A negative family history and abnormal DMRs in GNAS led to a diagnosis of sporadic PHP-1b of the patient.

Conclusions
Hypokalemia is a rare disorder associated with PHP-1b. Analysis of genetic and epigenetic mutations can aid in the diagnosis and accurate subtyping of PHP.
Factors associated with a reduced food intake after third molar extraction among adults: a cross-sectional study
Authors: Taniguchi Shinichi , Abe Atsushi , Ito Yu , Ishihama Takanori , Hayashi Hiroki , Momokita Moeko , Naito Ryuta , Shibata Kanae 
Published: April 2022

Abstract
Background
Functional impairment after third molar extraction may decrease the food intake. Elucidation of associated factors will contribute to a more appropriate postoperative nutritional management, and was the aim of the present study.

Methods
Adults aged < 60 years who were admitted for an extraction of one or more mandibular third molars were included. Those with diabetes mellitus, anemia, metabolic diseases, mental retardation, altered dietary intake, and postoperative paralysis of the lower lip and tongue were excluded. Patient-specific risk factors were compared in relation to a decrease in the food intake on postoperative day 1. Multivariate analysis took into account the patients’ background factors.

Results
A total of 254 patients were included (median age: 26.8 ± 9.3 years, 142 women); 508 third molars were extracted. Postoperative dietary intake reduction was more common (p < 0.05) after an exclusively mandibular extraction (16.0%) than after an extraction including the maxilla (29.4%). The reduction was also more common (p < 0.05) for an extraction difficulty of Pell–Gregory class III (39.5%) than for extraction difficulties of Pell–Gregory classes I (22.6%) and II (21.3%). The reduction was also more common (p < 0.05) in patients who experienced postoperative pain (66.7%) than in those who did not (23.3%). Significant differences were observed in sex (women: 34.5%, men: 11.6%) and age (young patients [< 26 years]: 31.1%, adult patients [≥ 26 years]: 17.2%); however, no significant difference was found in terms of experiencing trismus (p < 0.11). Simple regression analysis showed significant differences between patients who did and did not have a reduced postoperative food intake depending on the sex, age, extraction site, degree of extraction difficulty, trismus, and postoperative pain. Reduced dietary intake was significantly associated with sex (odds ratio [OR]: 0.30; 95% confidence interval [CI]: 0.14–0.38), age (OR: 1.6; 95% CI: 1.0–2.5), extraction site (OR: 0.51; 95% CI: 0.31–0.83), difficulty of extraction (OR: 0.66; 95% CI: 0.50–0.88), and postoperative pain (OR: 0.12; 95% CI: 0.04–0.37).

Conclusions
A younger age, female sex, extraction including the maxilla with deep implantation, and complaints of pain on postoperative day 1 were factors associated with a decreased food intake after third molar extraction.
Crossword puzzle as a learning tool to enhance learning about anticoagulant therapeutics
Authors: Bawazeer Ghada , Sales Ibrahim , Albogami Huda , Aldemerdash Ahmed , Mahmoud Mansour , Aljohani Majidah A. , Alhammad Abdullah 
Published: April 2022

AbstractBackgroundEducational games make the learning process more enjoyable, fun, and create a competitive classroom environment that can positively affect learning. The purpose of this study was to evaluate pharmacy students’ perceptions of crossword puzzles (CWPs) as a learning tool in the pharmacotherapy cardiovascular module focusing on anticoagulants’ therapeutics and assessing if students’ preference of learning style influenced their perception.MethodsClues for the puzzle were developed, validated, and piloted by course faculty. A free internet puzzle generator was used to create puzzles with 10 to 20 clues. Students were given 30 min to solve the puzzle following six hours of didactic lectures about the topic. An 8-item survey instrument and Pharmacists’ Inventory of Learning Styles (PILS) questionnaire were administered to examine students’ perceptions of the game and their learning style preference, respectively.ResultsTwo hundred sixty-seven students participated in the activity from both undergraduate programs (BPharm and PharmD) over three consecutive course offerings. Most students expressed favorable perceptions of the puzzle. Female and BPharm students had significantly more favorable perceptions than male and PharmD students on several perception items. The dominant preferred learning style (PLS) was converger (35.6%), followed by assimilator (25.3%), while 15.1% had mixed learning styles. The study did not find a significant association between PLS and students’ perceptions toward the CWP.ConclusionsThe CWP game presented an innovative, creative, and easy active learning tool to enhance information recall, retention, and class engagement while accommodating all learning style preferences.
What ethical approaches are used by scientists when sharing health data? An interview study
Authors: Viberg Johansson Jennifer , Bentzen Heidi Beate , Mascalzoni Deborah 
Published: April 2022

Abstract
Background
Health data-driven activities have become central in diverse fields (research, AI development, wearables, etc.), and new ethical challenges have arisen with regards to privacy, integrity, and appropriateness of use. To ensure the protection of individuals’ fundamental rights and freedoms in a changing environment, including their right to the protection of personal data, we aim to identify the ethical approaches adopted by scientists during intensive data exploitation when collecting, using, or sharing peoples’ health data.

Methods
Twelve scientists who were collecting, using, or sharing health data in different contexts in Sweden, were interviewed. We used systematic expert interviews to access these scientists’ specialist knowledge, and analysed the interviews with thematic analysis. Phrases, sentences, or paragraphs through which ethical values and norms were expressed, were identified and coded. Codes that reflected similar concepts were grouped, subcategories were formulated, and categories were connected to traditional ethical approaches.

Results
Through several examples, the respondents expressed four different ethical approaches, which formed the main conceptual categories: consideration of consequences, respect for rights, procedural compliance, and being professional.

Conclusions
To a large extent, the scientists’ ethical approaches were consistent with ethical and legal principles. Data sharing was considered important and worth pursuing, even though it is difficult. An awareness of the complex issues involved in data sharing was reflected from different perspectives, and the respondents commonly perceived a general lack of practical procedures that would by default ensure ethical and legally compliant data collection and sharing. We suggest that it is an opportune time to move on from policy discussions to practical technological ethics-by-design solutions that integrate these principles into practice.
Evaluation of a cross-sectoral care intervention for families with psychosocial burden: a study protocol of a controlled trial
Authors: Metzner Gloria , Horstmann Sabine , Barth Michael , Giesler Jürgen M. , Jünemann Susanne , Kaier Klaus , Schlett Christian , Schroeder Nora , Siebolds Marcus , Sinss Frank , van Staa Juliane , Glattacker Manuela , Renner Ilona 
Published: April 2022

Abstract
Background
Family risk factors, e.g. low socioeconomic status or parental mental health disorders, can affect children’s health and development. Thus, targeted preventive services for families with psychosocial burden are crucial. The German Early Childhood Intervention (ECI) program is a preventive approach that aims to strengthen parent’s resources by supportive services. However, research has revealed that only a proportion of the families considered to have substantial risk factors access the ECI program. To increase pediatricians’ skills in identifying risk factors, and to improve the cross-sectoral collaboration between relevant professionals and the referral of families to supportive services, the PATH-intervention (Pediatric Attention To Help) was developed. The PATH-intervention includes interprofessional quality circles and a one-day training program for the pediatricians. This study aims to evaluate this complex cross-sectoral care intervention for families with psychosocial burden.

Methods
Using a prospective quasi-experimental, controlled (matched-pair), longitudinal mixed-method design, we will compare families under treatment of pediatricians trained in the PATH-intervention with families under treatment of a control group of pediatricians. Participating families are asked to complete online-surveys. As a primary outcome, we will examine the use of supportive services of the ECI by burdened families. Secondary outcomes are the proportion of correctly identified families with psychosocial burden by the pediatricians, as well as information provision and motivation of the families to use the supportive services. Additionally, the cost-effectiveness ratio will be investigated. In the process evaluation, we will qualitatively explore the acceptance of the PATH-intervention of all involved stakeholders and the treatment fidelity of the trained pediatricians.

Discussion
This study will determine whether the PATH-intervention enables the pediatricians to identify and recommend supportive services to burdened families, as well as the families’ use of the supportive services of the ECI. Qualitative data will give insight into the acceptance of the intervention from the perspective of all stakeholders and the treatment fidelity. Results of this study could be the starting point for the broader implementation of the PATH-intervention as standard care.

Trial registration
German Clinical Trials Register (DRKS): DRKS00023461 (3rd December 2020); WHO UTN: U1111- 260-6575.
High activity and high functional connectivity are mutually exclusive in resting state zebrafish and human brains
Authors: Zarei Mahdi , Xie Dan , Jiang Fei , Bagirov Adil , Huang Bo , Raj Ashish , Nagarajan Srikantan , Guo Su 
Published: April 2022

Abstract
Background
The structural connectivity of neurons in the brain allows active neurons to impact the physiology of target neuron types with which they are functionally connected. While the structural connectome is at the basis of functional connectome, it is the functional connectivity measured through correlations between time series of individual neurophysiological events that underlies behavioral and mental states. However, in light of the diverse neuronal cell types populating the brain and their unique connectivity properties, both neuronal activity and functional connectivity are heterogeneous across the brain, and the nature of their relationship is not clear. Here, we employ brain-wide calcium imaging at cellular resolution in larval zebrafish to understand the principles of resting state functional connectivity.

Results
We recorded the spontaneous activity of >12,000 neurons in the awake resting state forebrain. By classifying their activity (i.e., variances of ΔF/F across time) and functional connectivity into three levels (high, medium, low), we find that highly active neurons have low functional connections and highly connected neurons are of low activity. This finding holds true when neuronal activity and functional connectivity data are classified into five instead of three levels, and in whole brain spontaneous activity datasets. Moreover, such activity-connectivity relationship is not observed in randomly shuffled, noise-added, or simulated datasets, suggesting that it reflects an intrinsic brain network property. Intriguingly, deploying the same analytical tools on functional magnetic resonance imaging (fMRI) data from the resting state human brain, we uncover a similar relationship between activity (signal variance over time) and functional connectivity, that is, regions of high activity are non-overlapping with those of high connectivity.

Conclusions
We found a mutually exclusive relationship between high activity (signal variance over time) and high functional connectivity of neurons in zebrafish and human brains. These findings reveal a previously unknown and evolutionarily conserved brain organizational principle, which has implications for understanding disease states and designing artificial neuronal networks.
Combined obstructive airflow limitation associated with interstitial lung diseases (O-ILD): the bad phenotype ?
Authors: Guiot Julien , Henket Monique , Frix Anne-Noëlle , Gester Fanny , Thys Marie , Giltay Laurie , Desir Colin , Moermans Catherine , Njock Makon-Sébastien , Meunier Paul , Corhay Jean-Louis , Louis Renaud 
Published: April 2022

Abstract
Background
Patients suffering from combined obstructive and interstitial lung disease (O-ILD) represent a pathological entity which still has to be well clinically described. The aim of this descriptive and explorative study was to describe the phenotype and functional characteristics of a cohort of patients suffering from functional obstruction in a population of ILD patients in order to raise the need of dedicated prospective observational studies and the evaluation of the impact of anti-fibrotic therapies.

Methods
The current authors conducted a retrospective study including 557 ILD patients, with either obstructive (O-ILD, n = 82) or non-obstructive (non O-ILD, n = 475) pattern. Patients included were mainly males (54%) with a mean age of 62 years.

Results
Patients with O-ILD exhibited a characteristic functional profile with reduced percent predicted forced expired volume in 1 s (FEV1) [65% (53–77) vs 83% (71–96), p < 0.00001], small airway involvement assessed by maximum expiratory flow (MEF) 25/75 [29% (20–41) vs 81% (64–108), p < 0.00001], reduced sGaw [60% (42–75) vs 87% (59–119), p < 0.01] and sub-normal functional residual capacity (FRC) [113% (93–134) vs 92% (75–109), p < 0.00001] with no impaired of carbon monoxide diffusing capacity of the lung (DLCO) compared to those without obstruction. Total lung capacity (TLC) was increased in O-ILD patients [93% (82–107) vs 79% (69–91), p < 0.00001]. Of interest, DLCO sharply dropped in O-ILD patients over a 5-year follow-up. We did not identify a significant increase in mortality in patients with O-ILD. Interestingly, the global mortality was increased in the specific sub-group of patients with O-ILD and no progressive fibrosing ILD phenotype and in those with connective tissue disease associated ILD especially in case of rheumatoid arthritis.

Conclusions
The authors individualized a specific functional-based pattern of ILD patients with obstructive lung disease, who are at risk of increased mortality and rapid DLCO decline over time. As classically those patients are excluded from clinical trials, a dedicated prospective study would be of interest in order to define more precisely treatment response of those patients.
MicroRNA-146a promotes proliferation, migration, and invasion of HepG2 via regulating FLAP
Authors: Wang Huihui , Zhang Shubing , Li Tao , Wang Lianzi , Lv Wei , Wang Shanshan , Ma Dongyue , Zang Yan , Zhu Xinyue , Xu Yuanhong , Zheng Lan , Shen Jilong , Wei Wei 
Published: April 2022

AbstractAbnormal expression of 5-Lipoxygenase Activating Protein (FLAP) has been detected in many tumor cells. MicroRNAs (miRNAs) negatively regulate gene expression post-transcriptionally by binding to the 3'–untranslated region (3'–UTR) of the target mRNA sequences and have been shown to be involved in various types of cancers. Herein, we aimed to demonstrate the expression of miR-146a and FLAP in human HCC tissues and liver cancer cell lines. We demonstrated that miR-146a expression is overexpressed, while FLAP protein and mRNA are suppressed in hepatocellular carcinoma tissues and HepG2 cells compared to para-carcinoma tissues and HL–7702 cells. Dual luciferase reporter gene assay showed that miR-146a-5p can directly target FLAP mRNA. Knockdown of miR-146a also resulted in increased FLAP expression of cancer cells. Additionally, miR-146a silencing or restoration of FLAP led to a reduction of HepG2 cell proliferation, cell cycle progression, migration, and invasion. This study showed that miR-146a has a stimulatory role in HepG2 cells and promotes HepG2 cell migration and invasion by targeting FLAP mRNA. Thus, miR-146a may be a tumor promoter and a potential therapeutic target for the treatment of HCC patients.
Proteolysis-targeting chimeras (PROTACs) in cancer therapy
Authors: Li Xinyi , Pu Wenchen , Zheng Qingquan , Ai Min , Chen Song , Peng Yong 
Published: April 2022

AbstractProteolysis-targeting chimeras (PROTACs) are engineered techniques for targeted protein degradation. A bifunctional PROTAC molecule with two covalently-linked ligands recruits target protein and E3 ubiquitin ligase together to trigger proteasomal degradation of target protein by the ubiquitin-proteasome system. PROTAC has emerged as a promising approach for targeted therapy in various diseases, particularly in cancers. In this review, we introduce the principle and development of PROTAC technology, as well as the advantages of PROTACs over traditional anti-cancer therapies. Moreover, we summarize the application of PROTACs in targeting critical oncoproteins, provide the guidelines for the molecular design of PROTACs and discuss the challenges in the targeted degradation by PROTACs.
Mitigating psychological distress in healthcare workers as COVID-19 waves ensue: a repeated cross-sectional study from Jordan
Authors: Obeidat Nour A. , Dodin Yasmeen I. , Hawari Feras I. , Albtoosh Asma S. , Manasrah Rasha M. , Mansour Asem H. 
Published: April 2022

AbstractBackgroundJordan has experienced several COVID-19 waves in the past 2 years. Cross-sectional studies have been conducted to evaluate distress in healthcare practitioners (HCPs), but there is limited evidence with regards to the impact of continuing pandemic waves on levels of distress in HCPs. We previously studied psychological distress in HCPs during the start of the pandemic (period 1, when cases were infrequent and the country was in lockdown), and demonstrated that HCPs were experiencing considerable stress, despite the country reporting low caseloads at the time. In this study, we sought to utilize the same methodology to reexamine levels of distress as COVID-19 peaked in the country and HCPs began managing large numbers of COVID-19 cases (period 2).MethodsA cross-sectional online survey utilizing a tool previously used during period 1 was completed by HCPs working in various settings. Demographic, professional and psychological factors such as distress, anxiety, depression, burnout, sleep issues, exhaustion, and fear were assessed; and coping strategies also were measured. Items in the tool were assessed for reliability and validity. A multivariable regression was used to identify factors that continued to impact distress during period 2.ResultsSamples in both periods (n = 937,n = 876, respectively) were relatively comparable in demographic characteristics, but in period 2, a greater proportion of nurses and healthcare practitioners reported working in general hospitals. During the pandemic peak (period 2), 49.0% of HCPs reported high levels of distress (compared to 32% in period 1); anxiety and depression scores were approximately 21% higher in period 2; and 50.6% reported fatigue (compared to 34.3% in period 1). Variables significantly associated with greater distress in period 2 included experiencing burnout, experiencing sleep disturbances, being fatigued, having fatalistic fears, and having fears related to workload. Conversely, being male, reporting satisfaction at work, and using positive coping practices were associated with a significantly lower odds of being in distress.ConclusionsBetween the two periods (early pandemic and first wave), COVID-19-related mental health continued to deteriorate among HCPs, highlighting the need to do more to support HCP front-liners facing COVID-19 surges.