bluuebunny/crossref_metadata_2025_split huggingface dataset:
Incremental burden of comorbid major depressive disorder in patients with type 2 diabetes or cardiovascular disease: a retrospective claims analysis
Authors: Kangethe Anne , Lawrence Debra F. , Touya Maëlys , Chrones Lambros , Polson Michael , Evangelatos Themmi 
Published: August 2021

Abstract
Background
The estimated prevalence of comorbid major depressive disorder (.
MDD) is 11% in patients with type 2 diabetes (T2D) and 15–20% in those with cardiovascular disease (CVD). Comorbid MDD continues to be a significant source of economic burden to the healthcare system.

Methods
We assessed the incremental healthcare burden of comorbid MDD in patients with T2D or CVD. This real-world, retrospective, administrative claims study analyzed commercially insured adults with T2D or CVD diagnosed on at least 2 separate claims within 12 months of each other (between January 1, 2011, and September 30, 2018). CVD included congestive heart failure, peripheral vascular disease, coronary heart disease, and cerebrovascular disease. The study compared patients with and without MDD with either T2D or CVD. Study assessments included all-cause healthcare resource utilization (proportion of patients with hospitalization, emergency department [ED] visits, and outpatient visits) and cost.

Results
Patients were matched by propensity score for demographics and baseline characteristics, resulting in similar baseline characteristics for the respective subcohorts. After matching, 22,892 patients with T2D (11,446 each with and without MDD) and 28,298 patients with CVD (14,149 each with and without MDD) were included.
At follow-up, patients with T2D and MDD had significantly higher rates of hospitalization (26.1% vs 17.4%, P < 0.0001) and ED visits (55.3% vs 43.0%, P < 0.0001) than those observed in patients without MDD. The total cost for patients with T2D and MDD at follow-up was significantly higher than for those without MDD ($16,511 vs $11,550, P < 0.0001). Similarly, at follow-up, patients with CVD and MDD had significantly higher rates of hospitalization (45.4% vs 34.1%, P < 0.0001) and ED visits (66.5% vs 55.4%, P < 0.0001) than those observed in patients without MDD. Total cost at follow-up for patients with CVD and MDD was significantly higher than for those without MDD ($25,546 vs $18,041, P < 0.0001).

Conclusions
Patients with either T2D or CVD and comorbid MDD have higher total all-cause healthcare utilization and cost than similar patients without MDD. Study findings reinforce the need for appropriate management of MDD in patients with these comorbid diseases, which in turn may result in cost reductions for payers.

Trial registration
Not applicable.
Adverse childhood experiences and child mental health: an electronic birth cohort study
Authors: Lowthian Emily , Anthony Rebecca , Evans Annette , Daniel Rhian , Long Sara , Bandyopadhyay Amrita , John Ann , Bellis Mark A. , Paranjothy Shantini 
Published: August 2021

Abstract
Background
Adverse childhood experiences (ACEs) are negatively associated with a range of child health outcomes. In this study, we explored associations between five individual ACEs and child mental health diagnoses or symptoms. ACEs included living with someone who had an alcohol-related problem, common mental health disorder or serious mental illness, or experienced victimisation or death of a household member.

Methods
We analysed data from a population-level electronic cohort of children in Wales, UK, (N = 191,035) between the years of 1998 and 2012. We used Cox regression with discrete time-varying exposure variables to model time to child mental health diagnosis during the first 15 years of life. Child mental health diagnoses include five categories: (i) externalising symptoms (anti-social behaviour), (ii) internalising symptoms (stress, anxiety, depression), (iii) developmental delay (e.g. learning disability), (iv) other (e.g. eating disorder, personality disorders), and (v) any mental health diagnosis, which was created by combining externalising symptoms, internalising symptoms and other. Our analyses were adjusted for social deprivation and perinatal risk factors.

Results
There were strong univariable associations between the five individual ACEs, sociodemographic and perinatal factors (e.g. gestational weight at birth) and an increased risk of child mental health diagnoses. After adjusting for sociodemographic and perinatal aspects, there was a remaining conditional increased risk of any child mental health diagnosis, associated with victimisation (conditional hazard ratio (cHR) 1.90, CI 95% 1.34–2.69), and living with an adult with a common mental health diagnosis (cHR 1.63, CI 95% 1.52–1.75). Coefficients of product terms between ACEs and deprivation were not statistically significant.

Conclusion
The increased risk of child mental health diagnosis associated with victimisation, or exposure to common mental health diagnoses, and alcohol problems in the household supports the need for policy measures and intervention strategies for children and their families.
Effect of local ozone treatment on rats with anterior rectal resection and the possible mechanisms
Authors: Zhang Wei , Wu Meng , Chen Peng , Zhang Jiamin , Ma Jiaze , Cheng Yile , Li Xiaoliu , Hu Junjie , Li Wanli , Du Yuxin , Ding Kang , Fan Zhimin 
Published: August 2021

Abstract
Background
Anterior resection syndrome (ARS) is characterized by the diverse and interchangeable evacuatory symptoms that may occur following distal colorectal resection. We aimed to investigate the effect and potential mechanisms of ozone perfusion on rats with anterior rectal resection (ARR).

Material and methods
After establishment of rat ARR model, 20, 40 and 80 ug/ml ozone was used to treat rats by enema administration. The pathological examination of intestinal tissue was detected using hematoxylin–eosin staining. The rate of loose stools, minimum threshold volume of abdominal withdrawal reflex (AWR) and Bristol grade were used to evaluate the degree of abnormal defecation function. Subsequently, the levels of oxidative stress- and inflammation-related markers, 5-hydroxytryptamine (5-HT), inducible nitric oxide synthase (iNOS) and nitric oxide (NO) in the serum and intestinal tissue were determined with the corresponding kits. Meanwhile, the expression of nuclear factor kappa B (NF-κB) p65, transient receptor potential vanilloid (TRPV)1, TRPV4, iNOS and 5-HT receptor 3A (5-HTR3A) was determined with RT-qPCR and western blotting.

Results
Ozone administration (20 and 40 ug/ml) significantly alleviated the pathological changes of intestinal tissue-induced by ARR, accompanied by the decreased loose stools rate, Bristol score and increased abdominal withdraw reflex. However, 80 ug/ml of ozone intervention played opposite roles in the aforementioned changes with 20 and 40 ug/ml of ozone. Additionally, remarkably elevated reactive oxygen species (ROS), malonaldehyde (MDA), superoxide dismutase (SOD), 5-HT, iNOS and NO levels were observed in the ozone-treated groups (20 and 40 ug/ml), while high dose of ozone drastically improved ROS, MDA, 5-HT, iNOS and NO levels but reduced the activity of SOD. Consistently, the contents of inflammatory factors were decreased after low and middle doses of ozone administration. However, high dose of ozone aggravated the inflammatory injury. Moreover, 20 and 40 ug/ml ozone upregulated TRPV1 and TRPV4 expression but downregulated 5-HTR3A expression, which was restored after 80 ug/ml of ozone intervention. Remarkably, the levels of NF-κB p65 and iNOS were dose-dependently enhanced following ozone treatment.

Conclusions
Taken together, low concentration of ozone attenuated intestinal injury induced by ARR via balancing oxidative stress and inflammation, but high concentration of ozone exacerbated the intestinal injury, which might be related to the 5-HT and TRPV signaling.
Pregnancy exposure of titanium dioxide nanoparticles causes intestinal dysbiosis and neurobehavioral impairments that are not significant postnatally but emerge in adulthood of offspring
Authors: Su Junhao , Duan Xinhao , Qiu Yu , Zhou Lixiao , Zhang Hongyang , Gao Min , Liu Yijun , Zou Zhen , Qiu Jingfu , Chen Chengzhi 
Published: August 2021

Abstract
Background
Pregnancy exposure to titanium dioxide nanoparticles (TiO2NPs) is a vital consideration due to their inadvertent ingestion from environmental contamination. The potential health effects of TiO2NPs on the neurodevelopmental process should be seriously concerned in health risk assessment, especially for the pregnant women who are susceptible to the neurodevelopmental toxicity of nano-sized particles. However, the available evidence of neurodevelopmental toxicity of TiO2NPs remains very limited.

Methods
In the present study, the pregnant mice were intragastric administered with 150 mg/kg TiO2NPs from gestational day (GD) 8 to 21, the maternal behaviors and neurodevelopment-related indicators in offspring were all assessed at different time points after delivery. The gut microbial community in both dams and their offspring were detected by using 16S ribosomal RNA (rRNA) gene sequencing. The gut-brain axis related indicators were also determined in the offspring.

Results
The results clearly demonstrated that exposure to TiO2NPs did not affect the maternal behaviors of pregnant mice, or cause the deficits on the developmental milestones and perturbations in the early postnatal development of offspring. Intriguingly, our data revealed that pregnancy exposure of TiO2NPs did not affect locomotor function, learning and memory ability and anxiety-like behavior in offspring at postnatal day (PD) 21, but resulted in obvious impairments on these neurobehaviors at PD49. Similar phenomena were obtained in the composition of gut microbial community, intestinal and brain pathological damage in offspring in adulthood. Moreover, the intestinal dysbiosis induced by TiO2NPs might be highly associated with the delayed appearance of neurobehavioral impairments in offspring, possibly occurring through disruption of gut-brain axis.

Conclusions
This is the first report elucidated that pregnancy exposure to TiO2NPs caused delayed appearance of neurobehavioral impairments in offspring when they reached adulthood, although these perturbations did not happen at early life after delivery. These findings will provide valuable insights about neurodevelopmental toxicity of TiO2NPs, and call for comprehensive health risk assessment of TiO2NPs on the susceptible population, such as pregnant women.

Graphical abstract
pH-sensitive dual drug loaded janus nanoparticles by oral delivery for multimodal analgesia
Authors: Liu Lin , Yao Wendong , Xie Xiaowei , Gao Jianqing , Lu Xiaoyang 
Published: August 2021

Abstract
Background
Based on the concept of “multimodal analgesia”, a novel dual drug delivery system was designed to achieve synergistic analgesia between najanajaatra venom protein (αCT) and resveratrol (Res). In order to meet the joint loading of two drugs with different physicochemical properties without affecting each other, an oral Janus nanoparticle (JNP) with a unique cavity structure and synergistic drug delivery was constructed using an improved double emulsion solvent evaporation method, and combined with low-molecular-weight chitosan/sodium alginate and PLGA to achieve its pH-responsive.

Results
The synthesized αCT/Res-JNPs are homogeneous in shape, with a two-compartment structure, approximately 230 nm in size, and zeta potential of 23.6 mV. Drug release assayed in vitro show that JNP was stable in simulated gastric juice (pH = 1.2) but was released in phosphate buffer saline (pH = 7.4). After intragastric administration in rats, PK evaluation showed that αCT/Res-JNPs could significantly improve the oral bioavailability, and the simultaneous encapsulation of the two drugs had no significant interaction on PK parameters. An obvious synergistic analgesic effects of αCT/Res-JNPs was confirmed in a spinal cord injury and acute pain model. Confocal laser scanning microscopy and single-pass intestinal perfusion model provided strong evidence that αCT/Res-JNPs could pass through intestinal epithelial cells, and the endocytosis pathway was mainly involved in the mediation and pinocytosis of reticulin. The concentrations of αCT and Res from αCT/Res-JNP in lymphatic transport were only about 8.72% and 6.08% of their blood concentrations at 1 h, respectively, which indicated that lymphatic transport in the form of JNP has limited advantages in improving the oral bioavailability of Res and αCT. Cellular uptake efficiency at 4 h was about 10–15% in Caco-2 cell lines for αCT/Res-JNP, but was reduced to 7% in Caco-2/HT29-MTX co-culture models due to the hindrance by the mucus layers. Approximately 12–17% of αCT/Res-JNP were transported across Caco-2/HT29-MTX/Raji monolayers. The cumulative absorption of JNP in three cell models was higher than that of free drug.

Conclusions
This study investigated the contribution of Janus nanoparticles in oral absorption, and provide a new perspective for oral administration and analgesic treatment of dual drug delivery system containing peptide drugs.

Graphic Abstract
Calcium signaling in hepatitis B virus infection and its potential as a therapeutic target
Authors: Kong Fanyun , Zhang Fulong , Liu Xiangye , Qin Suping , Yang Xiaoying , Kong Delong , Pan Xiucheng , You Hongjuan , Zheng Kuiyang , Tang Renxian 
Published: August 2021

AbstractAs a ubiquitous second messenger, calcium (Ca2+) can interact with numerous cellular proteins to regulate multiple physiological processes and participate in a variety of diseases, including hepatitis B virus (HBV) infection, which is a major cause of hepatitis, fibrosis, cirrhosis, and hepatocellular carcinoma. In recent years, several studies have demonstrated that depends on the distinct Ca2+ channels on the plasma membrane, endoplasmic reticulum, as well as mitochondria, HBV can elevate cytosolic Ca2+ levels. Moreover, within HBV-infected cells, the activation of intracellular Ca2+ signaling contributes to viral replication via multiple molecular mechanisms. Besides, the available evidence indicates that targeting Ca2+ signaling by suitable pharmaceuticals is a potent approach for the treatment of HBV infection. In the present review, we summarized the molecular mechanisms related to the elevation of Ca2+ signaling induced by HBV to modulate viral propagation and the recent advances in Ca2+ signaling as a potential therapeutic target for HBV infection.
Applications of various range shifters for proton pencil beam scanning radiotherapy
Authors: Lin Haibo , Shi Chengyu , Huang Sheng , Shen Jiajian , Kang Minglei , Chen Qing , Zhai Huifang , McDonough James , Tochner Zelig , Deville Curtiland , Simone Charles B. , Both Stefan 
Published: August 2021

AbstractBackgroundA range pull-back device, such as a machine-related range shifter (MRS) or a universal patient-related range shifter (UPRS), is needed in pencil beam scanning technique to treat shallow tumors.MethodsThree UPRS made by QFix (Avondale, PA, USA) allow treating targets across the body: U-shaped bolus (UB), anterior lateral bolus (ALB), and couch top bolus. Head-and-neck (HN) patients who used the UPRS were tested. The in-air spot sizes were measured and compared in this study at air gaps: 6 cm, 16 cm, and 26 cm. Measurements were performed in a solid water phantom using a single-field optimization pencil beam scanning field with the ALB placed at 0, 10, and 20 cm air gaps. The two-dimensional dose maps at the middle of the spread-out Bragg peak were measured using ion chamber array MatriXX PT (IBA-Dosimetry, Schwarzenbruck, Germany) located at isocenter and compared with the treatment planning system.ResultsA UPRS can be consistently placed close to the patient and maintains a relatively small spot size resulting in improved dose distributions. However, when a UPRS is non-removable (e.g. thick couch top), the quality of volumetric imaging is degraded due to their high Z material construction, hindering the value of Image-Guided Radiation Therapy (IGRT). Limitations of using UPRS with small air gaps include reduced couch weight limit, potential collision with patient or immobilization devices, and challenges using non-coplanar fields with certain UPRS. Our experience showed the combination of a U-shaped bolus exclusively for an HN target and an MRS as the complimentary device for head-and-neck targets as well as for all other treatment sites may be ideal to preserve the dosimetric advantages of pencil beam scanning proton treatments across the body.ConclusionWe have described how to implement UPRS and MRS for various clinical indications using the PBS technique, and comprehensively reviewed the advantage and disadvantages of UPRS and MRS. We recommend the removable UB only to be employed for the brain and HN treatments while an automated MRS is used for all proton beams that require RS but not convenient or feasible to use UB.
Health care transition for patients with vascular malformations: a French multicenter cross-sectional study
Authors: Vermersch Camille , Boccara Olivia , Chiaverini Christine , Mazereeuw-Hautier Juliette , Sigg Nina , Mallet Stéphanie , Vabres Pierre , Herbreteau Denis , Le Touze Anne , Maruani Annabel , Leducq Sophie ,   Research Group of the Société Française de Dermatologie Pédiatrique (French Society of Pediatric Dermatology)
Published: August 2021

Abstract
Background
Health care transition (i.e., transition from pediatric to adult care) is challenging in chronic conditions but has been poorly studied in rare chronic skin diseases. We investigated the proportion of lost to follow-up among patients with superficial vascular malformations after health care transition. We also collected patients’ opinions. This prospective, multicenter, cross-sectional study was performed at 7 French hospitals. We included patients aged 19–25 years, who were followed for a superficial vascular malformation before age 16, and who had completed the transition period in 2020. Data were collected from medical records and a questionnaire was sent to included patients asking about the health care transition.

Results
Among the 90 patients included, 41 (46%) were lost to follow-up after health care transition period. The age at diagnosis was significantly higher for lost to follow-up than non- lost to follow-up patients. The lost to follow-up proportion was similar between patients who changed and did not change hospitals during the transition. Responses to the questionnaire were obtained for 47 of 90 patients (52.2% response rate); most were satisfied with their care (n = 31/36, 86.1%); however, a lack of psychological support was reported.

Conclusions
Health care transition is associated to a high rate of lost to follow-up. Early management seems associated to less lost to follow-up. Further studies are needed to better understand risk factors for a failed health care transition and its consequences.
Expert opinion on diagnosing, treating and managing patients with cerebrotendinous xanthomatosis (CTX): a modified Delphi study
Authors: Stelten Bianca M. L. , Dotti Maria Teresa , Verrips Aad , Elibol Bülent , Falik-Zaccai Tzipora C. , Hanman Kate , Mignarri Andrea , Sithole Belina , Steiner Robert D. , Verma Surabhi , Yahalom Gilad , Zubarioglu Tanyel , Mochel Fanny , Federico Antonio 
Published: August 2021

AbstractBackgroundCerebrotendinous xanthomatosis (CTX) is a rare, chronic, progressive, neurodegenerative disorder requiring life-long care. Patients with CTX often experience a diagnostic delay. Although early diagnosis and treatment initiation can improve symptoms and prognosis, a standardised approach to diagnosis, treatment and management of patients is not yet established.AimTo assess expert opinion on best care practices for patients with CTX using a modified Delphi method.MethodsA multidisciplinary group of healthcare professionals with expertise in CTX responded to a 3-round online questionnaire (n = 10 in Rounds 1 and 2; n = 9 in Round 3), containing questions relating to the diagnosis, treatment, monitoring, multidisciplinary care and prognosis of patients with CTX. Determination of consensus achievement was based on a pre-defined statistical threshold of ≥ 70% Delphi panellists selecting 1–2 (disagreement) or 5–6 (agreement) for 6-point Likert scale questions, or ≥ 70% Delphi panellists choosing the same option for ranking and proportion questions.ResultsOf the Round 1 (n = 22), Round 2 (n = 32) and Round 3 (n = 26) questions for which consensus was assessed, 59.1%, 21.9% and 3.8% reached consensus, respectively. Consensus agreement that genetic analyses and/or determination of serum cholestanol levels should be used to diagnose CTX, and dried bloodspot testing should facilitate detection in newborns, was reached. Age at diagnosis and early treatment initiation (at birth, where possible) were considered to have the biggest impact on treatment outcomes. All panellists agreed that chenodeoxycholic acid (CDCA) is a lifetime replacement therapy which, if initiated early, can considerably improve prognosis as it may be capable of reversing the pathophysiological process in CTX. No consensus was reached on the value of cholic acid therapy alone. Monitoring patients through testing plasma cholestanol levels and neurologic examination was recommended, although further research regarding monitoring treatment and progression of the disease is required. Neurologists and paediatricians/metabolic specialists were highlighted as key clinicians that should be included in the multidisciplinary team involved in patients’ care.ConclusionsThe results of this study provide a basis for standardisation of care and highlight key areas where further research is needed to inform best practices for the diagnosis, treatment and management of patients with CTX.