bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluating the structural reform of outpatient psychotherapy in Germany (ES-RiP trial) - a qualitative study of provider perspectives
Authors: Poß-Doering Regina , Hegelow Martin , Borchers Milena , Hartmann Mechthild , Kruse Johannes , Kampling Hanna , Heuft Gereon , Spitzer Carsten , Wild Beate , Szecsenyi Joachim , Friederich Hans-Christoph 
Published: November 2021

Abstract
Background
Access to outpatient mental healthcare can be challenging for patients. In Germany, a national structural reform was implemented in 2017 to accelerate and enhance access to outpatient psychotherapy and reduce waiting times. During the first phase of the study ‘Evaluation of a structural reform of the outpatient psychotherapy guideline (ES-RiP)’ and embedded into a process evaluation, the implementation was to be evaluated through assessing general practitioners’ (GPs) and psychotherapists’ (PTs) perspectives regarding utilization of provided new measures, and perceived potential for optimization. Particular focus was on patients with a comorbidity of mental disorders and chronic physical conditions (cMPs).

Methods
This exploratory cross-sectional qualitative study used on-site and online focus group discussions and semi-structured telephone interviews with GPs and outpatient PTs. Generated data were analyzed using thematic framework analysis. Descriptive statistics were used to analyze participant characteristics collected via a socio-demographic questionnaire.

Results
Perspectives on the structural reform were heterogenous. GPs and PTs considered the component of timely initial psychotherapeutic assessment consultations beneficial. GPs disapproved of their deficits in detailed information about the structural reform and exchange with outpatient PTs. Improvement suggestions included structured short information exchange and joint quality circles. The overall number of available outpatient PTs in rural areas was perceived as insufficient. For patients with cMPs, GPs saw patient barriers for therapy access and continuity in low intrinsic motivation, physical impediments and older age. PTs also saw patient challenges regarding low intrinsic motivation and keeping scheduled appointments. They considered post-reform administrative efforts to be high and reported that the regulations (conformity) lead to planning difficulties and financial losses. Reform elements were tailored to fit in with PTs key therapy areas. Stronger networking and joint lectures were suggested as remedy for the currently still limited exchange with GPs. Unlike the GPs, PTs emphasized that accepting patients into psychotherapeutic treatment was independent of a possibly present chronic physical disease.

Conclusions
The findings contribute to understanding the integration of the delivered structural reform into daily care processes and provide an indication about reached targets and potential improvements. Further phases of the ES-RiP study can build on the findings and broaden insights.

Trial registration
Registration-ID DRKS00020344 (DRKS German Register of Clinical Trials.
Length of exposure to long working hours and night work and risk of sickness absence: a register-based cohort study
Authors: Peutere Laura , Rosenström Tom , Koskinen Aki , Härmä Mikko , Kivimäki Mika , Virtanen Marianna , Ervasti Jenni , Ropponen Annina 
Published: November 2021

Abstract
Background
There is inconsistent evidence that long working hours and night work are risk factors for sickness absence, but few studies have considered variation in the length of exposure time window as a potential source of mixed findings. We examined whether the association of long working hours and night work with sickness absence is dependent on the length of exposure to the working hour characteristics.

Methods
We analysed records of working hours, night work and sickness absence for a cohort of 9226 employees in one hospital district in Finland between 2008 and 2019. The exposure time windows ranged from 10 to 180 days, and we used Cox’s proportional hazards models with time-dependent exposures to analyse the associations between working-hour characteristics and subsequent sickness absence.

Results
Longer working hours for a period of 10 to 30 days was not associated with the risk of sickness absence whereas longer working hours for a period of 40 to 180 days was associated with a lower risk of sickness absence. Irrespective of exposure time window, night work was not associated with sickness absence.

Conclusions
It is important to consider the length of exposure time window when examining associations between long working hours and sickness absence, whereas the association between night work and sickness absence is not similarly sensitive to exposure times.
Placenta mediates the effect of maternal hypertension polygenic score on offspring birth weight: a study of birth cohort with fetal growth velocity data
Authors: Sato Noriko , Fudono Ayako , Imai Chihiro , Takimoto Hidemi , Tarui Iori , Aoyama Tomoko , Yago Satoshi , Okamitsu Motoko , Mizutani Shuki , Miyasaka Naoyuki 
Published: November 2021

Abstract
Background
Low birth weight (LBW) and fetal growth restriction are associated with the development of cardio-metabolic diseases later in life. A recent Mendelian randomization study concluded that the susceptibility of LBW infants to develop hypertension during adulthood is due to the inheritance of hypertension genes from the mother and not to an unfavorable intrauterine environment. Therein, a negative linear association has been assumed between genetically estimated maternal blood pressure (BP) and birth weight, while the observed relationship between maternal BP and birth weight is substantially different from that assumption. As many hypertension genes are likely involved in vasculature development and function, we hypothesized that BP-increasing genetic variants could affect birth weight by reducing the growth of the placenta, a highly vascular organ, without overtly elevating the maternal BP.

Methods
Using a birth cohort in the Japanese population possessing time-series fetal growth velocity data as a target and a GWAS summary statistics of BioBank Japan as a base data, we performed polygenic score (PGS) analyses for systolic BP (SBP), diastolic BP, mean arterial pressure, and pulse pressure. A causal mediation analysis was performed to assess the meditation effect of placental weight on birth weight reduced by maternal BP-increasing PGS. Maternal genetic risk score constituted of only “vasculature-related” BP single nucleotide polymorphisms (SNPs) was constructed to examine the involvement of vascular genes in the mediation effect of placental weight. We identified gestational week in which maternal SBP-increasing PGS significantly decreased fetal growth velocity.

Results
We observed that maternal SBP-increasing PGS was negatively associated with offspring birth weight. A causal mediation analysis revealed that a large proportion of the total maternal PGS effect on birth weight was mediated by placental weight. The placental mediation effect was remarkable when genetic risk score was constituted of “vasculature-related” BP SNPs. The inverse association between maternal SBP PGS and fetal growth velocity only became apparent in late gestation.

Conclusions
Our study suggests that maternal hypertension genes are strongly associated with placental growth and that fetal growth inhibition is induced through the intrauterine environment established by the placenta.
ciRS-7 is a prognostic biomarker and potential gene therapy target for renal cell carcinoma
Authors: Mao Weipu , Wang Keyi , Xu Bin , Zhang Hui , Sun Si , Hu Qiang , Zhang Lei , Liu Chunhui , Chen Shuqiu , Wu Jianping , Chen Ming , Li Wei , Peng Bo 
Published: November 2021

AbstractCircular RNAs are a new class of non-coding RNAs that have been shown to play critical roles in the development and progression of renal cell carcinoma (RCC). However, little is known about the functional mechanisms and therapeutic role of ciRS-7 in RCC. A series of in vitro and in vivo experiments were performed to investigate the functional mechanism and therapeutic role of ciRS-7, such as real-time quantitative PCR, CCK-8, wound healing, transwell, colony formation, Edu, tumor xenograft and lung metastasis in NSG mice. RNA pull-down, dual luciferase reporter, fluorescence in situ hybridization (FISH) and rescue assays were used to determine the relationship between ciRS-7, miR-139-3p and TAGLN. In addition, we constructed PBAE/si-ciRS-7 nanocomplexes with PBAE material to evaluate the therapeutic effect of the nanocomplexes on tumor in vivo. ciRS-7 was highly expressed in RCC tumor tissues and cell lines, and high ciRS-7 expression correlated with tumor size, high Fuhrman grade and poor survival. Depletion of ciRS-7 significantly inhibited RCC cell proliferation, invasion, tumor growth and metastasis in vivo, while overexpression of ciRS-7 had the opposite effect. Mechanistically, ciRS-7 acts as a "ceRNA" for miR-139-3p to prevent TAGLN degradation and promoting RCC progression and metastasis via the PI3K/AKT signaling pathway. In addition, miR-139-3p mimics or inhibitor could reverse the altered malignant tumor behavior caused by ciRS-7 overexpression or silencing. Furthermore, the PBAE/siciRS-7 nanocomplexes could significantly inhibit RCC tumor progression and metastasis in vivo. ciRS-7 acts as a tumor promoter by regulating the miR-139-3p/TAGLN axis and activating the PI3K/AKT signaling pathway to promote RCC progression and metastasis. Drug development of PBAE/si-ciRS-7 nanocomplexes targeting ciRS-7 may represent a promising gene therapeutic strategy for RCC.
Pregnancy-related complications and perinatal outcomes following progesterone supplementation before 20 weeks of pregnancy in spontaneously achieved singleton pregnancies: a systematic review and meta-analysis
Authors: Wu Hanglin , Zhang Songying , Lin Xiaona , He Jing , Wang Shasha , Zhou Ping 
Published: November 2021

Abstract
Background
Progesterone supplementation is widely performed in women with threatened miscarriage or a history of recurrent miscarriage; however, the effects of early progesterone supplementation on pregnancy-related complications and perinatal outcomes in later gestational weeks remain unknown.

Methods
Ovid MEDLINE, the Cochrane Library, Embase and ClinicalTrials.gov were searched until April 3rd, 2021. Randomized controlled trials regarding spontaneously achieved singleton pregnancies who were treated with progestogen before 20 weeks of pregnancy and were compared with those women in unexposed control groups were selected for inclusion. We performed pairwise meta-analyses with the random-effects model. The risk of bias was assessed according to the Cochrane Collaboration tool. The primary outcomes included preeclampsia (PE), and gestational diabetes mellitus (GDM), with the results presented as odds ratios (ORs) with 95% confidence intervals (CIs).

Results
We identified nine eligible studies involving 6439 participants. The pooled OR of subsequent PE following early progestogen supplementation was 0.64 (95% CI 0.42–0.98, moderate quality of evidence). A lower OR for PE was observed in the progestogen group when the subgroup analysis was performed in the vaginal subgroup (OR 0.62, 95%CI 0.40–0.96). There was insufficient evidence of a difference in the rate of GDM between pregnant women with early progestogen supplementation and unexposed pregnant women (OR 1.02, 95% CI 0.79–1.32, low quality of evidence). The pooled OR of low birth weight (LBW) following oral dydrogesterone was 0.57 (95% CI 0.34–0.95, moderate quality of evidence). The results were affected by a single study and the total sample size of enrolled women did not reach the required information size.

Conclusion
Use of vaginal micronized progesterone (Utrogestan) in spontaneously achieved singleton pregnancies with threatened miscarriage before 20 weeks of pregnancy may reduce the risk of PE in later gestational weeks. Among spontaneously achieved singleton pregnancies with threatened miscarriage or a history of recurrent miscarriage, use of oral dydrogesterone before 20 weeks of pregnancy may result in a lower risk of LBW in later gestational weeks. However, the available data were not sufficient to reach definitive conclusions, which highlighted the need for future studies.
Fibrinolytic markers could be useful predictors of severity in patients with pulmonary arterial hypertension: a retrospective study
Authors: Shoji Makoto , Matsui Taiju , Tanaka Hideaki , Nomura Kosuke , Tsujita Hiroaki , Kodama Yusuke , Koba Shinji , Kobayashi Youichi , Shinke Toshiro 
Published: November 2021

Abstract
Background
The severity of pulmonary arterial hypertension (PAH) is classified based on mean pulmonary artery pressure (mPAP) levels. However, other markers have not been elucidated. Fibrinolytic markers, such as total plasminogen activator inhibitor-1 (tPAI-1) and thrombomodulin (TM), are known to reflect arterial endothelial function. However, the relationship between serum tPAI-1, TM and pulmonary circulation has not been completely determined.

Methods
This study included 100 consecutive patients (38 men), with a mean age of 68.9 ± 12.0 years, with cardiac diseases who underwent right heart catheterization. Serum coagulation and fibrinolytic marker levels were measured.

Results
The average mPAP value was 25.1 ± 13.1 mmHg for all patients. The mPAP levels revealed a significant positive correlation with serum tPAI-1 (ρ = 0.24, p = 0.042) and uric acid (ρ = 0.29, p = 0.0031) levels. In the group with mPAP levels less than 25 mmHg (n = 58, ave. 17.3 ± 4.3 mmHg), mPAP levels showed a significant positive correlation with serum tPA-1 (ρ = 0.34, p = 0.034) and TM (ρ = 0.34, p = 0.043) values. The mean tPAI-1 (29.8 ± 23.3 ng/ml, p = 0.047) and uric acid (5.7 ± 1.8 mg/dl, p = 0.026) levels were significantly less in those with lower mPAP levels. A multivariate analysis revealed that tPAI-1 alone was a significant independent characteristic marker of PAH (odds ratio 1.02, 95%CI 1.000–1.036, p = 0.034).

Conclusions
These results indicate that serum tPAI-1 and TM may be useful predictors of severity, similar to mPAP in patients with PAH. They could be beneficial in predicting PAH among patients in the early stage of the disease.
GLRX5-associated [Fe-S] cluster biogenesis disorder: further characterisation of the neurological phenotype and long-term outcome
Authors: Sankaran Bindu Parayil , Gupta Sachin , Tchan Michel , Devanapalli Beena , Rahman Yusof , Procopis Peter , Bhattacharya Kaustuv 
Published: November 2021

Abstract
Background
Identification and characterisation of monogenic causes of complex neurological phenotypes are important for genetic counselling and prognostication. Bi-allelic pathogenic variants in the gene encoding GLRX5, a protein involved in the early steps of Fe-S cluster biogenesis, are rare and cause two distinct phenotypes: isolated sideroblastic anemia and a neurological phenotype with variant non-ketotic hyperglycinemia. In this study, we analysed the evolution of clinical and MRI findings and long-term outcome of patients with GLRX5 mutations.

Methods
Four patients from three Australian families of Lebanese descent were identified. All patients presented in childhood and were followed up into adult life through multiple clinical assessments. All were prescribed sodium benzoate.

Results
All patients (all females, age range 18–56 years) showed a complex neurological phenotype characterised by varying combinations of spastic paraparesis, length-dependent motor/sensory-motor axonal polyneuropathy, and psychiatric disturbances with variable intellectual disability. All had non-ketotic hyperglycinemia and a homozygous pathogenic c.151_153delAAG (p.K51del) change in GLRX5. Motor disability gradually progressed reaching moderate disability during adolescence and moderately severe disability during adult life. The major MRI finding was the upper cervical spinal cord signal changes with contrast enhancement noted in all and additional leukoencephalopathy in one. On follow up MRI, the white matter lesions diminished on a subsequent scan and then remained static over time. The spinal cord showed gliotic changes. Two patients have previously demonstrated low pyruvate dehydrogenase complex deficiency but none had plasma lactate elevation, nor biochemical evidence of branch-chain keto-dehydrogenase deficiency. Glycine levels reduced in patients that tolerated sodium benzoate, possibly stabilising clinical manifestations.

Conclusions
This report demonstrates that the p.K51del GLRX5 variant causes a distinct and predictable neurological phenotype. The clinical assessments spanning from childhood to adult life enable physicians to infer the natural history of GLRX5 related neurological disorder. There may be widespread metabolic consequences, and optimal management is unknown.
A cluster RCT and process evaluation of an implementation optimisation intervention to promote parental engagement enrolment and attendance in a childhood obesity prevention programme: results of the Optimising Family Engagement in HENRY (OFTEN) trial
Authors: Bryant Maria , Burton Wendy , Collinson Michelle , Farrin Amanda , Nixon Jane , Stevens June , Roberts Kim , Foy Robbie , Rutter Harry , Copsey Bethan , Hartley Suzanne , Tubeuf Sandy , Brown Julia 
Published: November 2021

Abstract
Background
Poor and variable implementation of childhood obesity prevention programmes reduces their population impact and sustainability. We drew upon ethnographic work to develop a multi-level, theory-based implementation optimisation intervention. This intervention aimed to promote parental enrolment and attendance at HENRY (Health Exercise Nutrition for the Really Young), a UK community obesity prevention programme, by changing behaviours of children’s centre and local authority stakeholders.

Methods
We evaluated the effectiveness of the implementation optimisation intervention on HENRY programme enrolment and attendance over a 12-month implementation period in a cluster randomised controlled trial. We randomised 20 local government authorities (with 126 children’s centres) to HENRY plus the implementation optimisation intervention or to HENRY alone. Primary outcomes were (1) the proportion of centres enrolling at least eight parents per programme and (2) the proportion of centres with a minimum of 75% of parents attending at least five of eight sessions per programme. Trial analyses adjusted for stratification factors (pre-randomisation implementation of HENRY, local authority size, deprivation) and allowed for cluster design. A parallel mixed-methods process evaluation used qualitative interviews and routine monitoring to explain trial results.

Results
Neither primary outcome differed significantly between groups; 17.8% of intervention centres and 18.0% of control centres achieved the parent enrolment target (adjusted difference − 1.2%; 95% CI − 19.5%, 17.1%); 17.1% of intervention centres and 13.9% of control centres achieved the attendance target (adjusted difference 1.2%; 95% CI − 15.7%, 18.1%). Unexpectedly, the trial coincided with substantial national service restructuring, including centre closures and reduced funds. Some commissioning and management teams stopped or reduced delivery of both HENRY and the implementation optimisation intervention due to competing demands. Thus, at follow-up, HENRY programmes were delivered to approximately half the number of parents compared to baseline (n = 433 vs. 881).

Conclusions
During a period in which services were reduced by external policies, this first definitive trial found no evidence of effectiveness for an implementation optimisation intervention promoting parent enrolment to and attendance at an obesity prevention programme.

Trial registration
ClinicalTrials.govNCT02675699. Registered on 4 February 2016
Spatial patterns of insect herbivory within a forest landscape: the role of soil type and forest stratum
Authors: Shao Xinliang , Zhang Qin , Yang Xitian 
Published: November 2021

Abstract
Background
Insect herbivory has profound impacts on ecosystem processes and services. Although many efforts have been made to recognize the main drivers of insect herbivory at different scales, the results are inconsistent. One likely reason is that studies have insufficiently captured the spatially heterogeneous factors such as soil type and forest stratum within the stand that may significantly affect insect herbivory. In particular, there is a lack of studies that address the detailed spatial patterns of insect herbivory which are influenced by these factors.

Methods
We measured the detailed spatial patterns of insect herbivory on cork oak (Quercus variabilis Bl.) in response to soil type (gravel soil and loam) and forest stratum (the upper, lower, and sapling stratum), and correlated these patterns with a set of influencing factors (litter coverage, coverage of shrubs and herbs, soil nutrients, soil moisture, and leaf traits) in a forest landscape.

Results
Generally, insect herbivory was spatially heterogeneous within stands. Herbivory was significantly lower in gravel soil areas than in loam soil areas and the highest herbivory occurred in the lower stratum. However, there were also 41 individual plots in which the highest herbivory occurred in the upper stratum and 29 plots in which the highest herbivory occurred in the sapling stratum. There were significant differences in soil nutrient and water status between soil types, but no significant differences in leaf traits. The effects of forest stratum on leaf traits were also inconsistent with those on insect herbivory.

Conclusions
Leaf traits may not be the main factors influencing insect herbivory in the field. Soil type may have major effects on herbivory patterns by influencing litter coverage while higher coverage of shrubs and herbs may reduce herbivory in the sapling stratum. These findings may advance our understanding of tree-herbivore interactions in real-world situations and have important implications for the sustainable management of forest ecosystems.
Retinal abnormalities in universal eye screening of healthy, full-term newborn infants in Jakarta. The incidence and its risk factors: a pilot study
Authors: Sitorus Rita S. , Pambudy Indra Maharddhika , Rohsiswatmo Rinawati , Barliana Julie Dewi , Yulia Dian Estu , Widyahening Indah Suci 
Published: November 2021

Abstract
Aim
To screen for ocular abnormalities in healthy full-term newborn infants using wide-field digital imaging and to analyze factors associated with the findings.

Methods
A total of 1208 full-term newborn infants at a tertiary eye hospital (Cipto Mangunkusumo National Referral Hospital) and a district hospital in Jakarta (Koja Hospital) were enrolled to the study. All eligible newborns underwent fundus examination within 48 h after birth using the RetCam shuttle (Natus Medical Incorporated, USA). Retinal findings were documented and analyzed according to obstetric and neonatal risk factors.

Results
Of the 1208 newborn infants enrolled, ocular abnormalities were found in 150 infants (12.4%). Retinal hemorrhage (RH) was the most common finding (88%) in which 2.67% involved the macula, followed by chorioretinitis (4.67%). Univariate analysis showed caesarean section (C-section) (OR 0.27, 95% CI 0.18–0.41, p < 0.001) was a protective factor against RH, while prolonged labor increased the risk of developing RH (OR 1.84, 95% CI 1.24–2.72, p = 0.002). Further multivariate analysis showed similar protective association between C-section and risk of RH (OR 0.29, 95% CI 0.19–0.44, p < 0.001), while other risk factors were not.

Conclusions
Our study showed that universal eye screening in healthy neonates is beneficial in the early diagnosis, monitoring and treatment of ocular abnormalities such as retinal hemorrhage, chorioretinitis and retinoblastoma. Retinal hemorrhage is the most common ocular abnormality and is associated with the delivery method and the duration of labor. Universal eye screening is visual-saving and life-saving for neonates with chorioretinitis, retinoblastoma as well as other abnormalities and should be mandatory in newborn screening.