bluuebunny/crossref_metadata_2025_split huggingface dataset:
The loss of DLG2 isoform 7/8, but not isoform 2, is critical in advanced staged neuroblastoma
Authors: Keane Simon , Martinsson Tommy , Kogner Per , Ejeskär Katarina 
Published: March 2021

Abstract
Background
Neuroblastoma is a childhood neural crest tumor showing large clinical and genetic heterogeneity, one form displaying 11q-deletion is very aggressive. It has been shown that 11q-deletion results in decreased expression of DLG2, a gene residing in the deleted region. DLG2 has a number of different isoforms with the main difference is the presence or absence of a L27 domain. The L27 domain containing DLG proteins can form complexes with CASK/MPP and LIN7 protein family members, which will control cell polarity and signaling.

Methods
We evaluated the DLG gene family and the LIN7 gene family for their expression in differently INSS staged neuroblastoma from publically available data and primary tumors, we included two distinct DLG1 and DLG2 N-terminal transcript isoforms encoding L27 domains for their expression. Functionality of DLG2 isoforms and of LIN7A were evaluated in the 11q-deleted neuroblastoma cell line SKNAS.

Results
In neuroblastoma only two DLG2 isoforms were expressed: isoform 2 and isoform 7/8. Using the array data we could determine that higher expression of DLG members that contain L27 domains correlated to better survival and prognosis. Whilst DLG1 showed a decrease in both isoforms with increased INSS stage, only the full length L27 containing DLG2 transcripts DLG2-isoform 7/8 showed a decrease in expression in high stage neuroblastoma. We could show that the protein encoded by DLG2-isoform 7 could bind to LIN7A, and increased DLG2-isoform 7 gene expression increased the expression of LIN7A, this reduced neuroblastoma cell proliferation and viability, with increased BAX/BCL2 ratio indicating increased apoptosis.

Conclusion
We have provided evidence that gene expression of the L27 domain containing DLG2-isoform 7/8 but not L27 domain lacking DLG2-isoform 2 is disrupted in neuroblastoma, in particular in the aggressive subsets of tumors. The presence of the complete L27 domain allows for the binding to LIN7A, which will control cell polarity and signaling, thus affecting cancer cell viability.
Systemic lupus Erythematosus and geomagnetic disturbances: a time series analysis
Authors: Stojan George , Giammarino Flavia , Petri Michelle 
Published: March 2021

Abstract
Background
To examine the influence of solar cycle and geomagnetic effects on SLE disease activity.

Methods
The data used for the analysis consisted of 327 observations of 27-day Physician Global Assessment (PGA) averages from January 1996 to February 2020. The considered geomagnetic indices were the AP index (a daily average level for geomagnetic activity), sunspot number index R (measure of the area of solar surface covered by spots), the F10.7 index (measure of the noise level generated by the sun at a wavelength of 10.7 cm at the earth’s orbit), the AU index (upper auroral electrojet index), and high energy (> 60 Mev) proton flux events. Geomagnetic data were obtained from the Goddard Space Flight Center Space Physics Data Facility. A time series decomposition of the PGA averages was performed as the first step. The linear relationships between the PGA and the geomagnetic indices were examined using parametric statistical methods such as Pearson correlation and linear regression, while the nonlinear relationships were examined using nonparametric statistical methods such as Spearman’s rho and Kernel regression.

Results
After time series deconstruction of PGA averages, the seasonality explained a significant fraction of the variance of the time series (R2 = 38.7%) with one cycle completed every 16 years. The analysis of the short-term (27-day) relationships indicated that increases in geomagnetic activity Ap index (p < 0.1) and high energy proton fluxes (> 60 Mev) (p < 0.05) were associated with decreases in SLE disease activity, while increases in the sunspot number index R anticipated decreases in the SLE disease activity expressed as PGA (p < 0.05). The short-term correlations became statistically insignificant after adjusting for multiple comparisons using Bonferroni correction. The analysis of the long-term (297 day) relationships indicated stronger negative association between changes in the PGA and changes in the sunspot number index R (p < 0.01), AP index (p < 0.01), and the F10.7 index (p < 0.01). The long-term correlations remained statistically significant after adjusting for multiple comparisons using Bonferroni correction.

Conclusion
The seasonality of the PGA averages (one cycle every 16 years) explains a significant fraction of the variance of the time series. Geomagnetic disturbances, including the level of geomagnetic activity, sunspot numbers, and high proton flux events may influence SLE disease activity. Studies of other geographic locales are needed to validate these findings.
“Drugs are a taboo”: a qualitative and retrospective study on the role of education and harm reduction strategies associated with the use of psychoactive substances under the age of 18
Authors: da Silva Gabriela Almeida Pinto , Pereira Catarina Pinto , Pinto Marta Sofia de Sousa 
Published: March 2021

Abstract
Background
The use of psychoactive substances frequently starts at a younger age than adulthood. Considering the perspective of young people, this retrospective study tried to provide them with a role in identifying their own needs regarding drug use and interventions focused on it; the obstacles in accessing both general health and harm reduction services; the changes needed for a more effective, congruent and empowering response to the use of psychoactive substances before the age of 18.

Methods
The study was divided into two parts having both parts a qualitative focus. In the first part of the study, an online questionnaire was sent to all harm reduction teams and two focus groups were carried out with eight harm reduction professionals and six people who use(d) drugs. The second part used an online questionnaire applied to 143 participants aged between the age of 18 and 25 complemented by two semi-structured interviews.

Results
The need for education about psychoactive substances, namely in the educational context; the lack of information about available services; and the need for confidentiality were the most mentioned issues by the young people. Also, the informal network played a significant role in the participants relationship with psychoactive substances.

Conclusions
The lack of information was the most highlighted obstacle. Also, there is a confluence of various vulnerabilities such as being under 18, using drugs and the different social situations that they live in. To improve policy and practice regarding drug use among young people, harm reduction interventions must be scaled-up as well as intentionally driven to empower youth to deal with. School environment was chosen by participants as one of the elected environments to implement harm reduction services.
A study protocol for a quasi-experimental community trial evaluating the integration of indigenous healing practices and a harm reduction approach with principles of seeking safety in an indigenous residential treatment program in Northern Ontario
Authors: Marsh T. N. , Eshakakogan C. , Eibl J. K. , Spence M. , Morin K. A. , Gauthier G. J. , Marsh D. C. 
Published: March 2021

AbstractBackgroundIndigenous communities in Canada face significant challenges with intergenerational trauma, which manifests in substance use disorders. There is consensus that connecting treatment approaches to culture, land, community, and spiritual practices is a pathway to healing trauma and substance use disorders for Indigenous peoples. Indigenous residential addiction treatment programs have been established as the primary intervention to provide healing for Indigenous peoples with substance use disorders and intergenerational trauma. However, there is limited evidence demonstrating the effectiveness of these programs. In collaboration with the Benbowopka Treatment Centre, this paper describes a study protocol which aims to evaluate the effectiveness of blending Indigenous Healing Practices and Seeking Safety for the treatment of Indigenous patients with intergenerational trauma and substance use disorders.MethodsWe will conduct a pre/post Quasi Experimental Community trial, to compare historical treatment outcomes for patients following the implementation of Indigenous Healing and Seeking Safety. We will conduct quantitative and qualitative analyses to understand the differences before and after the intervention is implemented. The pre- Indigenous Healing and Seeking Safety intervention study window will span from 2013 to 2016;n = 343, and the post-Indigenous Healing and Seeking Safety intervention study window from 2018 to 2020;n > 300. All participants will be enrolled in the Benbowopka residential treatment for the first time during the study periods. All data will be anonymized at the time of data entry. Propensity matching will be undertaken for patient characteristics, including sex/gender, age, and substance use type.Results and conclusionsThe study findings could be used to inform intergenerational trauma and substance use disorders residential treatment programming for Indigenous communities across Canada. Our work will contribute to the field of community-based intergenerational trauma and substance use disorders programming by addressing objectives that consider: (a) the patient perspective, (b) the program perspective, and (c) the community perspective. The study findings may validate an innovative approach for evaluating the effectiveness of residential addiction treatment and particularly the effective and appropriate care for Indigenous patients with intergenerational trauma and substance use disorders.
Detecting response shift in health-related quality of life measurement among patients with hypertension using structural equation modeling
Authors: Chen Hao , Zhu Lin , Zhou Rui , Liu Panpan , Lu Xiaoyang , Patrick Donald L. , Edwards Todd C. , Wang Hongmei 
Published: March 2021

Abstract
Background
Outcomes derived from longitudinal self-reported health-related quality of life measures can be confounded by response shift. This study was aimed to detect response shift among patients with hypertension attending a community-based disease management program.

Methods
240 consecutive consulting or follow-up patients with diagnosed hypertension were recruited. The Short Form 36-item Health Survey was self-administered at 12 community health service stations at baseline and four weeks after attending the program. The 4-step structural equation modeling approach assessed response shift.

Results
Data from 203 (84.6%) patients were eligible for analyses (mean age 65.9 ± 10.8 years, 46.3% female). The results showed uniform recalibration of social functioning ($${\upchi}_{\mathrm{SBdiff}}^{2}$$

χ

SBdiff

2

(1) = 22.98, P < 0.001), and non-uniform recalibration of role limitations due to physical problems ($${\upchi}_{\mathrm{SBdiff}}^{2}$$

χ

SBdiff

2

(1) = 8.84, P = 0.003), and bodily pain ($${\upchi}_{\mathrm{SBdiff}}^{2}$$

χ

SBdiff

2

(1) = 17.41, P < 0.001). The effects of response shift on social functioning were calculated as “small” (effect-size = 0.35), but changed the observed changes from improvement (effect-size = 0.25) to slight deterioration (effect-size = -0.10). After accounting for the response shift effect, the general physical health of participants was improved (effect-size = 0.37), while deterioration (effect-size = -0.21) in the general mental health was also found.

Conclusions
Recalibration existed among patients with hypertension attending the disease management program. The interventions in the program might act as a catalyst that induced the response shift. We conclude that response shift should be considered in hypertension research with longitudinal health-related quality of life data.
Psycho-sexual influence of sterilization on women’s quality of life: a path model
Authors: Youseflu Samaneh , Jahanian Sadatmahalleh Shahideh 
Published: March 2021

Abstract
Background
Tubal ligation, as a permanent contraception method, have a negative and positive impact on women’s life. This study aimed to test a conceptual model considering the interrelated role of menorrhagia, body image concern, self-esteem, sexual function, anxiety and depression on quality of life (QOL) of sterilized women.

Methods
The current study was conducted as a cross-sectional study on 200 sterilized women. Data were collected using a socio-demographic checklist, Short Form Health Survey (SF-12), pictorial blood loss assessment chart, female sexual function index, hospital anxiety and depression scale, body image concern inventory, and Rosenberg Self-esteem Scale. Data were analyzed using Pearson correlation coefficient and path analysis.

Results
Results show that anxiety, sexual function, self-esteem, and body image dissatisfaction have a direct effect on women’s QOL. Higher level of anxiety, and body dissatisfaction directly reduce QOL. Sexual function, and menorrhagia, with an indirect effect through anxiety, reduces QOL. Higher level of anxiety with indirect effect thorough self-esteem can worsen QOL. Also, sexual function indirectly affects QOL through anxiety.

Conclusion
It looks that the proposed predictors of this model are greatly important. These findings give support for a hypothetical model in which betterment in SF, body image satisfaction, self-esteem, anxiety, and menorrhagia led to a good QOL of sterilized women. Hence, in designing care for sterilized women, these factors should be considered.
A poorer nutritional status impacts quality of life in a sample population of elderly cancer patients
Authors: Rios Tatiane Correia , de Oliveira Lucivalda Pereira Magalhães , da Costa Maria Lúcia Varjão , da Silva Baqueiro Boulhosa Ramona Souza , Roriz Anna Karla Carneiro , Ramos Lilian Barbosa , Bueno Allain Amador 
Published: March 2021

Abstract
Rationale
Quality of Life (QoL) is impaired in cancer, and the elderly are particularly vulnerable to malnutrition. A diagnosis of cancer in elderly patients further exacerbates risks of negative health outcomes. Here we investigated associations between QoL and nutritional status in a sample population of mostly socially deprived elderly cancer patients.

Method
432 cancer patients were recruited for this cross-sectional study at point of admission to a tertiary referral hospital for cancer treatment. Patient-generated subjective global assessment (PG-SGA) assessed nutritional status. Functional assessment of cancer therapy- general (FACT-G) quantified QoL. Relationship between PG-SGA and QoL was assessed by Spearman correlation. PG-SGA outcomes were compared against FACT-G scores employing Mann–Whitney test. Bivariate Linear Regression Model was employed to investigate influences of sociodemographic, clinical and nutritional status upon QoL.

Results
37.5% of participants were malnourished or at risk. 39% were illiterate and 54.6% had family income lower than minimum wage. Malnourished patients showed lower FACT-G scores (76.8 vs. 84.7; p = 0.000). Poor nutritional diagnosis was inversely correlated with all QoL domains. Bivariate regression analysis showed that lower PG-SGA scores (βo =  − 1.00; p = 0.000) contributed to FACT-G score deterioration, the male gender showed better QoL scores, and other clinical and sociodemographic variables did not show relationship.

Conclusion
Poorer nutritional status was significantly associated with worsened physical, social, emotional and functional well-being QoL domains in elderly cancer patients. Poorer nutritional status is an independent risk factor for worsened QoL. Future policies aimed at particularly vulnerable populations may improve QoL and health outcomes.
Lupus anticoagulant hypoprothrombinemia syndrome associated with bilateral adrenal haemorrhage in a child: early diagnosis and intervention
Authors: Sakamoto Atsushi , Ogura Masao , Hattori Atsushi , Tada Kinji , Horikawa Reiko , Nakadate Hisaya , Matsumoto Kimikazu , Nogami Keiji , Ieko Masahiro , Ishiguro Akira 
Published: March 2021

Abstract
Background
Lupus anticoagulant-hypoprothrombinemia syndrome (LAHPS) is characterized by bleeding and thrombosis in patients with autoimmune diseases or infections. Paediatric LAHPS exhibits various degrees of bleeding, ranging from mild to severe; however, adrenal haemorrhage due to LAHPS and its long-term clinical course have not been sufficiently described.

Case presentation
A 9-year-old boy presented with prolonged abdominal pain and abnormal coagulation screening tests. The laboratory tests showed prolonged activated partial thromboplastin time and subsequently revealed the presence of lupus anticoagulant, anti-nuclear antibodies, and hypoprothrombinemia, leading to diagnosis of LAHPS. An enhanced computed tomogram demonstrated nodular lesions in the adrenal glands bilaterally, suggestive of adrenal haemorrhage. Laboratory and clinical manifestations exhibited life-threatening adrenal insufficiency that required hydrocortisone administration. The patient developed systemic lupus erythematosus, diagnosed 12 months later.

Conclusions
This patient with LAHPS developed rare adrenal failure due to adrenal haemorrhage, a life-threatening event that should be recognized and treated early. In our case, renal dysfunction was also observed when systemic lupus erythematosus was diagnosed 1 year after LAHPS. Our case emphasizes that early recognition of adrenal failure and careful long-term observation is required in patients with autoantibodies.
Cyclophosphamide use in treatment of refractory Kawasaki disease with coronary artery aneurysms
Authors: Halyabar Olha , Friedman Kevin G. , Sundel Robert P. , Baker Annette L. , Chang Margaret H. , Gould Patrick W. , Newburger Jane W. , Son Mary Beth F. 
Published: March 2021

Abstract
Background
Despite timely administration of IVIG, some patients with Kawasaki disease (KD) develop rapidly progressive or giant coronary artery aneurysms (CAA).

Case presentation
We describe our experience using cyclophosphamide (CYC) for the treatment of such cases as well as a review of the literature on the use of CYC in KD. Through a retrospective chart review of our KD population, we identified ten children treated for KD with intravenous CYC (10 mg/kg/dose) for one or two doses. Seven patients were male, the median age was 2.0 years (range 4 months − 5 years). All patients received initial IVIG between day 4–10 of illness. Other anti-inflammatory treatments administered before CYC included second IVIG (n = 9), corticosteroids (n = 10), infliximab (n = 4), cyclosporine (n = 2), and anakinra (n = 1). Median illness day at administration of the first CYC dose was 22.5 days (range:10–36 days). The primary indication for treatment with CYC for all patients was large or giant CAA and/or rapid progression of CAA. Three patients received a second dose of CYC (10 mg/kg) for progressively enlarging CAA. CAA did not progress after final CYC treatment. One patient with a history of neutropenia in infancy developed severe neutropenia 9 days after treatment with CYC, which recovered without intervention or complications. No patient developed infections or other serious toxicity from CYC.

Conclusion
In KD patients with severe and progressive enlargement of CAA despite anti-inflammatory therapy, CYC seemed to arrest further dilation and was well-tolerated. Future multicenter studies are needed to confirm our findings in this subgroup of KD patients.
A systemic immune challenge to model hospital-acquired infections independently regulates immune responses after pediatric traumatic brain injury
Authors: Sharma Rishabh , Zamani Akram , Dill Larissa K. , Sun Mujun , Chu Erskine , Robinson Marcus J. , O’Brien Terence J. , Shultz Sandy R. , Semple Bridgette D. 
Published: March 2021

Abstract
Background
Traumatic brain injury (TBI) is a major cause of disability in young children, yet the factors contributing to poor outcomes in this population are not well understood. TBI patients are highly susceptible to nosocomial infections, which are mostly acquired within the first week of hospitalization, and such infections may modify TBI pathobiology and recovery. In this study, we hypothesized that a peripheral immune challenge such as lipopolysaccharide (LPS)—mimicking a hospital-acquired infection—would worsen outcomes after experimental pediatric TBI, by perpetuating the inflammatory immune response.

Methods
Three-week-old male mice received either a moderate controlled cortical impact or sham surgery, followed by a single LPS dose (1 mg/kg i.p.) or vehicle (0.9% saline) at 4 days post-surgery, then analysis at 5 or 8 days post-injury (i.e., 1 or 4 days post-LPS).

Results
LPS-treated mice exhibited a time-dependent reduction in general activity and social investigation, and increased anxiety, alongside substantial body weight loss, indicating transient sickness behaviors. Spleen-to-body weight ratios were also increased in LPS-treated mice, indicative of persistent activation of adaptive immunity at 4 days post-LPS. TBI + LPS mice showed an impaired trajectory of weight gain post-LPS, reflecting a synergistic effect of TBI and the LPS-induced immune challenge. Flow cytometry analysis demonstrated innate immune cell activation in blood, brain, and spleen post-LPS; however, this was not potentiated by TBI. Cytokine protein levels in serum, and gene expression levels in the brain, were altered in response to LPS but not TBI across the time course. Immunofluorescence analysis of brain sections revealed increased glia reactivity due to injury, but no additive effect of LPS was observed.

Conclusions
Together, we found that a transient, infection-like systemic challenge had widespread effects on the brain and immune system, but these were not synergistic with prior TBI in pediatric mice. These findings provide novel insight into the potential influence of a secondary immune challenge to the injured pediatric brain, with future studies needed to elucidate the chronic effects of this two-hit insult.
HoMEcare aRm rehabiLItatioN (MERLIN): telerehabilitation using an unactuated device based on serious games improves the upper limb function in chronic stroke
Authors: Rozevink Samantha G. , van der Sluis Corry K. , Garzo Ainara , Keller Thierry , Hijmans Juha M. 
Published: March 2021

AbstractBackgroundHoMEcare aRm rehabiLItatioN (MERLIN) is an unactuated version of the robotic device ArmAssist combined with a telecare platform. Stroke patients are able to train the upper limb function using serious games at home. The aim of this study is to investigate the effect of MERLIN training on the upper limb function of patients with unilateral upper limb paresis in the chronic phase of stroke (> 6 months post stroke).MethodsPatients trained task specific serious games for three hours per week during six weeks using an unactuated version of a robotic device. Progress was monitored and game settings were tailored through telerehabilitation. Measurements were performed six weeks pre-intervention (T0), at the start (T1), end (T2) and six weeks post-intervention (T3). Primary outcome was the Wolf Motor Function Test (WMFT). Secondary outcomes were other arm function tests, quality of life, user satisfaction and motivation.ResultsTwelve patients were included, ten completed the training. From start of the intervention to six weeks follow up, WMFT improved significantly with 3.8 points (p = .006), which is also clinically relevant. No significant changes in quality of life were observed. Patients were overall satisfied with the usability of the device. Comfort and the robustness of the system need further improvements.ConclusionPatients in the chronic phase of stroke significantly improved their upper limb function with the MERLIN training at home.Trial registrationThis study is registered at the Netherlands Trial Register (NL7535). Registered 18–02-2019,https://www.trialregister.nl/trial/7535.