bluuebunny/crossref_metadata_2025_split huggingface dataset:
The influence of explainable vs non-explainable clinical decision support systems on rapid triage decisions: a mixed methods study
Authors: Laxar Daniel , Eitenberger Magdalena , Maleczek Mathias , Kaider Alexandra , Hammerle Fabian Peter , Kimberger Oliver 
Published: September 2023

Abstract
Background
During the COVID-19 pandemic, a variety of clinical decision support systems (CDSS) were developed to aid patient triage. However, research focusing on the interaction between decision support systems and human experts is lacking.

Methods
Thirty-two physicians were recruited to rate the survival probability of 59 critically ill patients by means of chart review. Subsequently, one of two artificial intelligence systems advised the physician of a computed survival probability. However, only one of these systems explained the reasons behind its decision-making. In the third step, physicians reviewed the chart once again to determine the final survival probability rating. We hypothesized that an explaining system would exhibit a higher impact on the physicians’ second rating (i.e., higher weight-on-advice).

Results
The survival probability rating given by the physician after receiving advice from the clinical decision support system was a median of 4 percentage points closer to the advice than the initial rating. Weight-on-advice was not significantly different (p = 0.115) between the two systems (with vs without explanation for its decision). Additionally, weight-on-advice showed no difference according to time of day or between board-qualified and not yet board-qualified physicians. Self-reported post-experiment overall trust was awarded a median of 4 out of 10 points. When asked after the conclusion of the experiment, overall trust was 5.5/10 (non-explaining median 4 (IQR 3.5–5.5), explaining median 7 (IQR 5.5–7.5), p = 0.007).

Conclusions
Although overall trust in the models was low, the median (IQR) weight-on-advice was high (0.33 (0.0–0.56)) and in line with published literature on expert advice. In contrast to the hypothesis, weight-on-advice was comparable between the explaining and non-explaining systems. In 30% of cases, weight-on-advice was 0, meaning the physician did not change their rating. The median of the remaining weight-on-advice values was 50%, suggesting that physicians either dismissed the recommendation or employed a “meeting halfway” approach. Newer technologies, such as clinical reasoning systems, may be able to augment the decision process rather than simply presenting unexplained bias.
LncRNA SLCO4A1-AS1 suppresses lung cancer progression by sequestering the TOX4-NTSR1 signaling axis
Authors: Chen Yi-Ling , Liu Yi-Nan , Lin Yen-Ting , Tsai Meng-Feng , Wu Shang-Gin , Chang Tzu-Hua , Hsu Chia-Lang , Wu Huey-Dong , Shih Jin-Yuan 
Published: September 2023

Abstract
Background
Metastasis is a multistep process involving the migration and invasion of cancer cells and is a hallmark of cancer malignancy. Long non-coding RNAs (lncRNAs) play critical roles in the regulation of metastasis. This study aims to elucidate the role of the lncRNA solute carrier organic anion transporter family member 4A1-antisense 1 (SLCO4A1-AS1) in metastasis and its underlying regulatory mechanisms.

Methods
A comprehensive analysis of the Gene Expression Omnibus (GEO) database were used to identify metastasis-associated lncRNAs. Transwell migration and invasion assays, and a tail vein-injection mouse model were used to assess the migration and invasion of cancer cells in vitro and in vivo, respectively. High-throughput screening methods, including MASS Spectrometry and RNA sequencing (RNA-seq), were used to identify the downstream targets of SLCO4A1-AS1. Reverse transcription quantitative polymerase chain reaction (RT-qPCR), western blotting, RNA pull-down, RNA immunoprecipitation (RIP), fluorescence in situ hybridization (FISH), and chromatin immunoprecipitation (ChIp) assays were conducted to identify and validate the underlying regulatory mechanisms of SLCO4A1-AS1.

Results
SLCO4A1-AS1 reduced cancer cell migration and invasion by disrupting cytoskeleton filaments, and was associated with longer overall survival in patients with lung adenocarcinoma. SLCO4A1-AS1 directly interacted with the DNA-binding protein, TOX High Mobility Group Box Family Member 4 (TOX4), to inhibit TOX4-induced migration and invasion. Furthermore, RNA-seq revealed that neurotensin receptor 1 (NTSR1) is a novel and convergent downstream target of SLCO4A1-AS1 and TOX4. Mechanistically, SLCO4A1-AS1 functions as a decoy of TOX4 by interrupting its interaction with the NTSR1 promoter and preventing NTSR1 transcription. Functionally, NTSR1 promotes cancer cell migration and invasion through cytoskeletal remodeling, and knockdown of NTSR1 significantly inhibits TOX4-induced migration and invasion.

Conclusion
These findings demonstrated that SLCO4A1-AS1 antagonizes TOX4/NTSR1 signaling, underscoring its pivotal role in lung cancer cell migration and invasion. These findings hold promise for the development of novel therapeutic strategies targeting the SLCO4A1-AS1/TOX4/NTSR1 axis as a potential avenue for effective therapeutic intervention in lung cancer.
International harm reduction indicators are still not reached: results from a repeated cross-sectional study on drug paraphernalia distribution in Germany, 2021
Authors: Hommes Franziska , Krings Amrei , Dörre Achim , Neumeier Esther , Schäffer Dirk , Zimmermann Ruth 
Published: September 2023

Abstract
Background
To prevent the transmission of blood-borne infections and reach the elimination of viral hepatitis by 2030, the World Health Organization (WHO) has set the goal to distribute 300 sterile needles and syringes each year per person who injects drugs (PWID). We aimed to assess drug paraphernalia distribution in Germany in 2021, including the WHO indicator, and to analyse changes to the distribution measured in 2018.

Methods
We conducted a repeated cross-sectional study of low-threshold drug services in Germany. We assessed type and quantity of distributed drug paraphernalia and the number of supplied PWID in 2021 using an online and paper-based questionnaire. We conducted a descriptive statistical analysis of data from 2021, assessed fulfillment of the WHO indicator and changes in services that participated 2021 and in the previous study 2018.

Results
Five hundred and eighty-nine of 1760 distributed questionnaires were returned in 2021. 204 drug services from 15 out of 16 federal states confirmed drug paraphernalia distribution, covering 20% of Germany’s rural and 51% of urban counties. 108 services had also participated in 2018. The most frequently distributed paraphernalia for injecting drug use in 2021 were syringes (97% of services), needles (96%) and vitamin C (90%). Pre-cut aluminium foil (79% of services) and pipes (28%) for inhaling, and sniff tubes (43%) for nasal use were distributed less frequently. We found a median reduction in distributed syringes by 18% and by 12% for needles compared to 2018. Of 15 states, two reached the 2030 WHO-target for needles and one for syringes.

Conclusions
The current national estimates and changes from 2018 to 2021 for drug paraphernalia distribution seem far from meeting the WHO target. Reasons could include a change in drug consumption behaviour towards less injecting use and more inhaling, and effects of the COVID-19 pandemic (supply difficulties, social distancing, lockdown, reduced opening hours of services). We observed pronounced regional differences in drug paraphernalia distribution. To close existing gaps, Germany should expand its drug paraphernalia distribution programmes and other harm reduction services, such as drug consumption rooms. Further investigation of determinants for adequate distribution is essential to reduce blood-borne infections in this key population.
Mitochondrial dysfunction at the crossroad of cardiovascular diseases and cancer
Authors: Rocca Carmine , Soda Teresa , De Francesco Ernestina Marianna , Fiorillo Marco , Moccia Francesco , Viglietto Giuseppe , Angelone Tommaso , Amodio Nicola 
Published: September 2023

AbstractA large body of evidence indicates the existence of a complex pathophysiological relationship between cardiovascular diseases and cancer. Mitochondria are crucial organelles whose optimal activity is determined by quality control systems, which regulate critical cellular events, ranging from intermediary metabolism and calcium signaling to mitochondrial dynamics, cell death and mitophagy. Emerging data indicate that impaired mitochondrial quality control drives myocardial dysfunction occurring in several heart diseases, including cardiac hypertrophy, myocardial infarction, ischaemia/reperfusion damage and metabolic cardiomyopathies. On the other hand, diverse human cancers also dysregulate mitochondrial quality control to promote their initiation and progression, suggesting that modulating mitochondrial homeostasis may represent a promising therapeutic strategy both in cardiology and oncology. In this review, first we briefly introduce the physiological mechanisms underlying the mitochondrial quality control system, and then summarize the current understanding about the impact of dysregulated mitochondrial functions in cardiovascular diseases and cancer. We also discuss key mitochondrial mechanisms underlying the increased risk of cardiovascular complications secondary to the main current anticancer strategies, highlighting the potential of strategies aimed at alleviating mitochondrial impairment-related cardiac dysfunction and tumorigenesis. It is hoped that this summary can provide novel insights into precision medicine approaches to reduce cardiovascular and cancer morbidities and mortalities.
Structural ultrasound of joints and tendons in healthy children: development of normative data
Authors: Wittoek Ruth , Decock Céline , Dewaele Nele , Arnold Lara , Baeyens Pieter , De Schrijver Ignace , Pardaens Lisa , Raftakis Ioannis , Renson Thomas , Rinkin Charline , Thooft Alexander D. J. , Vanhaverbeke Tine , Verbist Caroline 
Published: September 2023

Abstract
Background
Musculoskeletal ultrasound is a well accessible technique to assess disease activity in children with juvenile idiopathic arthritis. Knowledge of reference values of joint structures is indispensable to differentiate between physiological and pathological finding. The aim of this study was to assess the structural sonographic features of joints and tendons in healthy children from several age groups (0.2–18 year), and develop a set of normative data.

Methods
Greyscale ultrasound was performed in 500 healthy children (age 0.2–18 years) according to a predefined scanning protocol (Additional file 1) including the shoulder, elbow, wrist, second metacarpophalangeal joint, hip, knee, ankle, and first metatarsophalangeal joint). Demographic data and values of cartilage thickness, tendon diameters, and the degree of capsular distention measured by bone-capsular distance (BCD) were collected. Differences according to the sex were assessed by unpaired t-test. Single and multiple regression analyses were performed between the ultrasound outcomes and covariates such as age, height, weight and body mass index. Growth charts and tables were developed with respect to age. Nonparametric quantile regression was applied using the R-packages quantreg and quantregGrowth.

Results
A total of 195 male and 305 female volunteers were included between the age of 0 and 18 years (mean age 8.9; range: 0.2–17.9 years). Cartilage diminished markedly as children aged, and cartilage of the boys was significantly thicker compared to the girls in all joints (p < 0.001). In addition, cartilage became thinner as children’s height and weight increased (beta regression coefficients between − 0.27 and − 0.01, p < 0.0001). Capsular distention (i.e., BCD > 0 mm) was uncommon in the ankle, wrist and MCP2 (resp. in 3, 6, and 3% of cases). It was more common in the suprapatellar and parapatellar knee, MTP1 and posterior recess of the elbow (resp. in 34, 32, 46, and 39% of cases). In the hip, some capsular distention was always present. Age was found to be the best predictor for BCD (beta regression coefficients between 0.05 and 0.13, p < 0.0001). Height was, in addition to age, a good predictor of tendon diameter (beta regression coefficients between 0.03 and 0.14, p < 0.0001). Growth curves and tables for each variable were developed.

Conclusions
Reference values of sonographic cartilage thickness, BCD and diameters of tendons at several joints were established from 500 healthy children, aged between 0.2 and 18 years. Growth charts and tables were developed to distinguish normal findings from pathology in children with complaints suspicious of arthritis.
Transcranial magnetic stimulation and transcranial direct current stimulation affect explicit but not implicit emotion regulation: a meta-analysis
Authors: Qiu Xiufu , He Zhenhong , Cao Xueying , Zhang Dandan 
Published: September 2023

AbstractEmotion regulation (ER) refers to the process through which people influence the occurrence, experience, and expression of emotions. It can be established in an explicit (voluntary) or implicit (automatic) way, both of which are essential for mental and physical well-being. Recent evidence has highlighted the potential of transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS) targeting the prefrontal cortex (PFC) to modulate ER. However, previous studies have only evaluated the effects of TMS and tDCS on explicit ER, leaving implicit ER relatively unexplored. In this review and meta-analysis, we systematically evaluated the effects of TMS and tDCS over the PFC on the two forms of ER, using both subjective and physiological response as outcome indicators. Twenty-seven studies were included in our study. Both subjective (Hedges’ g = − 0.20) and physiological (Hedges’ g = − 0.65) results indicated a significant effect of TMS and tDCS targeting PFC on down-regulation of explicit ER, but not implicit ER (Hedges’ g = − 0.04). Moreover, moderation analysis indicated that the effect of TMS and tDCS on the down-regulating of subjective experience was moderated by several factors, including stimulation method, target area, target hemisphere, and stimulation timing. Specifically, our results showed that applying TMS or targeting the right PFC, particularly the right ventrolateral prefrontal cortex, or using offline TMS and tDCS produced a larger stimulation effect on ER. In summary, these findings suggest that TMS and tDCS has a positive effect on explicit, but not implicit ER. The distinct TMS and tDCS effect on the two forms of ER help deepen our understanding of TMS and tDCS use and provide valuable insights for the development of tailored TMS and tDCS protocols for explicit and implicit regulation.
Application of non-invasive prenatal testing to 91,280 spontaneous pregnancies and 3477 pregnancies conceived by in vitro fertilization
Authors: Wei Rong , Li Jingran , Xia Yuanyuan , Wang Chaohong , Lu Xinran , Fang Yuqin , Zhu Jiansheng 
Published: September 2023

Abstract
Background
Many clinical studies based on spontaneous pregnancies (SPs) have demonstrated the superiority of non-invasive prenatal testing (NIPT), and the question of whether this technology is suitable for offspring conceived by assisted reproductive technology has attracted attention. This study aimed to evaluate the application value of NIPT in screening for trisomy (T)21, T18, T13 and sex chromosome aneuploidy (SCA) in pregnant women who conceived by in vitro fertilization (IVF).

Results
In total, there were 804 high-risk cases [0.88% (804/91280), singleton = 795, twin = 9] in the SP group. Among the 558 invasive prenatal diagnosis (IPD) cases (singleton = 556, twin = 2), 343 (singleton = 342, twin = 1) were true positive, including 213 cases of T21, 28 of T18, 5 of T13 and 97 (singleton = 96, twin = 1) of SCA. The positive predictive values (PPVs) of T21, T18, T13, SCA and T21/T18/T13 combined in singleton pregnancy were 89.12% (213/239), 51.85% (28/54), 21.74% (5/23), 40.00% (96/240), and 77.85% (246/316), respectively, and the PPV of SCA in twin pregnancy was 100.00%. In the IVF group, IPD was performed in 19 (singleton = 16, twin = 3) of the 27 high-risk cases [0.78% (27/3477), singleton = 16, twin = 3], of which 9 (singleton = 8, twin = 1) were true positive, including 5 cases (singleton = 4, twin = 1) of T21 and 4 of SCA. The PPVs of singleton T21, SCA and T21/T18/T13 combined were 66.67% (4/6), 50.00% (4/8) and 57.14% (4/7), respectively, and the PPV of twin T21 was 100.00% (1/1). There were no significant differences in PPV among T21, SCA and T21/T18/T13 combined in singletons between the groups (89.12% vs. 66.67%, p = 0.09; 40.00% vs. 50.00%, p = 0.57; 77.85% vs. 57.14%, p = 0.20). The sensitivity and specificity were higher for singleton and twin pregnancies in the two groups. Based on follow-up results, 1 case of false negative T21 was found in the singleton SP group. Additionally, the mean foetal fraction (FF) of the IVF group was lower than that of the SP group (11.23% vs. 10.51%, p < 0.05).

Conclusion
NIPT has high sensitivity and specificity in screening chromosomal aneuploidies in both IVF pregnancy and spontaneous pregnancy, so it is an ideal screening method for IVF pregnancy.
Comparison of Huntington’s disease phenotype progression in male and female heterozygous FDNQ175 mice
Authors: Li Si Han , Colson Tash-Lynn L. , Chen Jingwei , Abd-Elrahman Khaled S. , Ferguson Stephen S. G. 
Published: September 2023

AbstractHuntington’s Disease (HD) is an inherited autosomal dominant neurodegenerative disorder that leads to progressive motor and cognitive impairment due to the expansion of a polyglutamine (CAG) repeat in the N-terminal region of the huntingtin (Htt) protein. The creation of HD mouse models represents a critical step in the research for HD treatment. Among the currently available HD mouse models, the zQ175 knock-in mouse line is the first to display robust disease phenotype on a heterozygous background. The newer FDNQ175 mouse model is derived from the zQ175 mouse line and presents a more aggressive phenotype. Moreover, increasing evidence has implicated sex as a contributing factor in the progression of HD symptoms. Here, we compared the progression of HD phenotypes in male and female heterozygous FDNQ175 mice. We found that both male and female heterozygous mice showed deficits in forelimb grip strength and cognition as early as 6 months of age. However, female FDNQ175 mice were less vulnerable to HD-associated decline in limb coordination and movement. Neither male nor female FDNQ175 mice exhibited reduced locomotor activity in the open field or exhibit consistent differences in anxiety at 6–12 months of age. Both male and female FDNQ175 mice exhibited increased numbers of huntingtin aggregates with age and 8-month-old female FDNQ175 mice had significantly more aggregates than their male counterparts. Taken together, our results provide further evidence that sex can influence the progression of HD phenotype in preclinical animal models and must be taken into consideration for future HD research.
Bronchiolitis guidelines: what about the Italian situation in a primary care setting?
Authors: Porcaro Federica , Cutrera Renato , Vittucci Anna Chiara , Villani Alberto 
Published: September 2023

AbstractAcute viral bronchiolitis is the most common cause of hospitalization in children under 12 months of age. The variable clinical presentation and the potential for sudden deterioration of the clinical conditions require a close monitoring by healthcare professionals.In Italy, first access care for children is provided by primary care physicians (PCPs) who often must face to a heterogeneous disease presentation that, in some cases, make the management of patient with bronchiolitis challenging. Consequently, Italian studies report poor adherence to national and international guidelines processed to guide the clinicians in decision making in acute viral bronchiolitis.This paper aims to identify the potential factors contributing to the lack of adherence to the suggested guidelines derived by clear and evidence-based recommendations among primary care physicians operating in an outpatient setting, with a specific focus on the context of Italy. Particularly, we focus on the prescription of medications such as β2-agonists, systemic steroids, and antibiotics which are commonly prescribed by PCPs to address conditions that can mimic bronchiolitis.
Protocol for a randomized control trial of the Building Regulation in Dual Generations Program (BRIDGE): preventing the intergenerational transmission of mental illness in at-risk preschool children
Authors: Penner-Goeke Lara , Belows Madeline , Kristjanson Amanda , Andrade Brendan F. , Cameron Emily E. , Giuliano Ryan , Katz Laurence Y. , Kelly Lauren E. , Letourneau Nicole , Mota Natalie , Reynolds Kristin , Zalewski Maureen , Pharazyn Ashley , Roos Leslie E. 
Published: September 2023

Abstract
Background
Since the onset of the COVID-19 pandemic, the worldwide prevalence of maternal depression has risen sharply; it is now estimated that one quarter of mothers experience clinically significant depression symptoms. Exposure to maternal depression during early childhood increases the risk for the development of childhood mental illness (MI) in offspring, with altered parenting practices mediating the association between maternal depression and child outcomes. Dual-generation interventions, which aim to simultaneously treat parent and child mental health, show promise for improving outcomes for mothers with depression and their young children. The Building Regulation in Dual Generations (BRIDGE) program combines Dialectical Behavior Therapy (DBT) and parenting skills training to concurrently treat maternal depression and improve parenting practices. In pilot within-group studies, BRIDGE has led to large reductions in maternal depression and child MI symptoms. The aim of the current study is to evaluate the efficacy of BRIDGE in reducing maternal depression and child MI symptoms (primary outcomes) as well as parenting stress and harsh parenting (secondary outcomes).

Methods
A three-armed randomized control trial with equal group sizes will be conducted to compare the efficacy of (1) BRIDGE (DBT + parenting skills), (2) DBT skills training, and (3) services-as-usual. Participants (n = 180) will be mothers of 3- to 5-year-old children who report elevated depression symptoms. Those randomized to BRIDGE or DBT skills training will complete a 16-week group therapy intervention. Assessments will be administered at pre-intervention(T1) post-intervention (T2), and 6-month follow-up (T3).

Discussion
Dual-generation programs offer an innovative approach to prevent the intergenerational transmission of mental illness. The current study will add to the evidence base for BRIDGE by comparing it to a stand-alone mental health intervention and a services-as-usual group. These comparisons will provide valuable information on the relative efficacy of including parenting support in a mental health intervention for parents. The results will contribute to our understanding of how maternal depression affects children’s development and how intervening at both a mental health and parenting level may affect child and family outcomes.

Trial registration
Name of registry: Clinical Trials Protocol Registration and Results System; trial registration number: NCT05959538; date of registry: July 24, 2023; available: https://classic.clinicaltrials.gov/ct2/show/NCT05959538