bluuebunny/crossref_metadata_2025_split huggingface dataset:
Integration of metabolites from meta-analysis with transcriptome reveals enhanced SPHK1 in PDAC with a background of pancreatitis
Authors: Ketavarapu Vijayasarathy , Ravikanth Vishnubhotla , Sasikala Mitnala , Rao G. V. , Devi Ch. Venkataramana , Sripadi Prabhakar , Bethu Murali Satyanarayana , Amanchy Ramars , Murthy H. V. V. , Pandol Stephen J. , Reddy D. Nageshwar 
Published: July 2022

Abstract
Background
Pathophysiology of transformation of inflammatory lesions in chronic pancreatitis (CP) to pancreatic ductal adenocarcinoma (PDAC) is not clear.

Methods
We conducted a systematic review, meta-analysis of circulating metabolites, integrated this data with transcriptome analysis of human pancreatic tissues and validated using immunohistochemistry. Our aim was to establish biomarker signatures for early malignant transformation in patients with underlying CP and identify therapeutic targets.

Results
Analysis of 19 studies revealed AUC of 0.86 (95% CI 0.81-0.91, P < 0.0001) for all the altered metabolites (n = 88). Among them, lipids showed higher differentiating efficacy between PDAC and CP; P-value (< 0.0001). Pathway enrichment analysis identified sphingomyelin metabolism (impact value-0.29, FDR of 0.45) and TCA cycle (impact value-0.18, FDR of 0.06) to be prominent pathways in differentiating PDAC from CP. Mapping circulating metabolites to corresponding genes revealed 517 altered genes. Integration of these genes with transcriptome data of CP and PDAC with a background of CP (PDAC-CP) identified three upregulated genes; PIGC, PPIB, PKM and three downregulated genes; AZGP1, EGLN1, GNMT. Comparison of CP to PDAC-CP and PDAC-CP to PDAC identified upregulation of SPHK1, a known oncogene.

Conclusions
Our analysis suggests plausible role for SPHK1 in development of pancreatic adenocarcinoma in long standing CP patients. SPHK1 could be further explored as diagnostic and potential therapeutic target.
Is RDW a clinically relevant prognostic factor for newly diagnosed multiple myeloma? A systematic review and meta-analysis
Authors: Chen Xiaomin , Liu Jiayue , Duan Jialin , Xiong Hao , Liu Yang , Zhang Xinwen , Huang Chunlan 
Published: July 2022

Abstract
Background
Multiple myeloma (MM) is an incurable plasma cell malignancy. Red cell distribution width (RDW) is a prognostic marker in various diseases, solid tumors, and hematologic neoplasms, but its prognostic significance in MM is controversial. In this study, we aimed to assess the relationship between RDW and the clinical prognosis of MM patients through a meta-analysis.

Methods
Relevant literature were retrieved from PubMed, Embase, and Web of Science databases according to PRISMA guideline. All relevant parameters were extracted and combined for statistical analysis. The effect size was presented as hazard ratio (HR)/odds ratio (OR) and 95% confidence interval (CI). HR/OR > 1 in MM patients with high RDW suggested a worse prognosis. Heterogeneity test evaluation was performed using Cochran's Q test and I2 statistics. A Pheterogeneity < 0.10 or I2 > 50% suggested significant heterogeneity. P < 0.05 was considered statistically significant. Statistical analysis was performed using Stata 12.0 software.

Results
8 articles involving 9 studies with 1165 patients were included in our meta-analysis. Our results suggested that elevated RDW is significantly associated with poor prognosis in MM (OS: HR = 1.91, 95%CI: 1.48–2.46; PFS: HR = 2.87, 95% CI: 2.02–4.07). A significant correlation was not found between RDW and International Staging System (ISS) staging (ISS III VS ISS I-II: OR:1.53; 95%CI:0.97–2.42).

Conclusion
Our results suggested that RDW is a robust predictor of newly diagnosed MM outcomes.
Feasibility and acceptability of a novel telepsychiatry-delivered precision prescribing intervention for anxiety and depression
Authors: O’Callaghan Erin , Sullivan Scott , Gupta Carina , Belanger Heather G. , Winsberg Mirène 
Published: July 2022

Abstract
Background
Major Depressive Disorder and Generalized Anxiety Disorder are pervasive and debilitating conditions, though treatment is often inaccessible and based on trial-and-error prescribing methods. The present observational study seeks to describe the use of a proprietary precision prescribing algorithm piloted during routine clinical practice as part of Brightside’s telepsychiatry services. The primary aim is to determine the feasibility and acceptability of implementing this intervention. Secondary aims include exploring remission and symptom improvement rates.

Methods
Participants were adult patients enrolled in Brightside who completed at least 12 weeks of treatment for depression and/or anxiety and received a prescription for at least one psychiatric medication. A prescription recommendation was made by Brightside’s algorithm at treatment onset and was utilized for clinical decision support. Participants received baseline screening surveys of the PHQ-9 and GAD-7, and at weeks 2,4,6,8,10 and 12. Intent-to-treat (ITT) sensitivity analyses were conducted. Feasibility of the implementation was measured by the platform’s ability to enroll and engage participants in timely psychiatric care, as well as offer high touch-point treatment options. Acceptability was measured by patient responses to a 5-star satisfaction rating.

Results
Brightside accessed and treated 6248 patients from October 2018 to April 2021, treating a majority of patients within 4-days of enrollment. The average plan cost was $115/month. 89% of participants utilized Brightside’s core medication plan at a cost of $95/month. 13.4% of patients in the study rated Brightside’s services as highly satisfactory, averaging a 4.6-star rating. Furthermore, 90% of 6248 patients experienced a MCID in PHQ-9 or GAD-7 score. Remission rates were 75% (final PHQ-9 or GAD-7 score < 10) for the study sample and 59% for the ITT sample. 69.3% of Brightside patients were treated with the medication initially prescribed at intake.

Conclusions
Results suggest that the present intervention may be feasible and acceptable within the assessed population. Exploratory analyses suggest that Brightside’s course of treatment, guided by precision recommendations, improved patients’ symptoms of anxiety and depression.
Comorbidity of adult ADHD and substance use disorder in a sample of inpatients bipolar disorder in Iran
Authors: Badrfam Rahim , Zandifar Atefeh , Barkhori Mehni Mahdi , Farid Malihe , Rahiminejad Fatemeh 
Published: July 2022

Abstract
Backgrounds
The study of the relationship between adult Attention deficit hyperactivity disorder (ADHD) and bipolar disorder has received more attention in recent years and there is limited information in this area. On the other hand, there is a significant comorbidity between ADHD and bipolar disorder with substance use disorder. In this study, we investigated the prevalence of comorbidity of adult ADHD and substance use disorder among a group of bipolar patients admitted to a psychiatric hospital.

Methods
One hundred fifty patients from a total of 200 consecutive patients who were referred to the emergency department of Roozbeh Psychiatric Hospital in Tehran, diagnosed with bipolar disorder based on the initial psychiatric interview and needed hospitalization, were evaluated again by an experienced faculty member psychiatrist by using a subsequent interview based on the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition(DSM-5).
They were evaluated using the Structured Clinical Interview for DSM-5 (SCID-5) questionnaire to confirm the diagnosis of bipolar disorder and the comorbidity of adult ADHD and substance use disorder.

Results
From 150 patients diagnosed with bipolar disorder, 106 patients (70.7%) had adult ADHD. 89 patients (59.3%) had substance use disorder and 58 patients (38.7%) had both of these comorbidities with bipolar disorder. Comorbidity of adult ADHD was associated with the earlier onset of the first mood episode in bipolar disorder (p value = 0.025). There was no statistically significant relationship between substance use disorder and age of onset of the first episode. (P value = 0.57).

Conclusions
Due to the limitations of studies on adult ADHD comorbidity with bipolar disorder, especially in hospital settings, as well as the increased risk of association with substance use disorder, further multicenter studies in this area with larger sample sizes can increase awareness in this regard.
Early (years) reactions: comparative analysis of early childhood policies and programs during the first wave of the COVID-19 pandemic
Authors: Kearon Joanne , Carsley Sarah , van den Heuvel Meta , Hopkins Jessica 
Published: July 2022

Abstract
Background
During the first wave of COVID-19 there was little evidence to guide appropriate child and family programs and policy supports.

Methods
We compared policies and programs implemented to support early child health and well-being during the first wave of COVID-19 in Australia, Canada, the Netherlands, Singapore, the UK, and the USA. Program and policy themes were focused on prenatal care, well-baby visits and immunization schedules, financial supports, domestic violence and housing, childcare supports, child protective services, and food security.

Results
Significant heterogeneity in implementation of OECD-recommended policy responses was found with all of the included countries implementing some of these policies, but no country implementing supports in all of the potential areas.

Conclusions
This analysis gives insight into initial government reactions to support children and families, and opportunities for governments to implement further supportive programs and policies during the current pandemic and future emergencies.
A qualitative examination of naloxone access in three states: Connecticut, Kentucky, and Wisconsin
Authors: Spector Antoinette L. , Galletly Carol L. , Christenson Erika A. , Montaque H. Danielle Green , Dickson-Gomez Julia 
Published: July 2022

Abstract
Background
Prevention of opioid-involved overdose deaths remains a public health priority in the United States. While expanding access to naloxone is a national public health strategy, it is largely implemented at the state and local level, where significant variability in policies, resources, and norms exist. The aims of the current study were to examine the social context of naloxone access in three different states (Connecticut, Kentucky, Wisconsin) from the perspectives of key informants (first responders, harm reduction personnel, and pharmacists), who play some role in dispensing or administering naloxone within their communities.

Methods
Interviews were conducted with key informants who were in different local areas (urban, suburban, rural) across Connecticut, Kentucky, and Wisconsin. Interview guides explored the key informants’ experiences with administering or dispensing naloxone, and their perspectives on opioid overdose prevention efforts in their areas. Data analysis was conducted using multistage inductive coding and comparative methods to identify dominant themes within the data.

Results
Key informants in each of the three states noted progress toward expanding naloxone access, especially among people who use opioids, but also described inequities. The key role of harm reduction programs in distributing naloxone within their communities was also highlighted by participants, as well as barriers to increasing naloxone access through pharmacies. Although there was general consensus regarding the effectiveness of expanding naloxone access to prevent overdose deaths, the results indicate that communities are still grappling with stigma associated with drug use and a harm reduction approach.

Conclusion
Findings suggest that public health interventions that target naloxone distribution through harm reduction programs can enhance access within local communities. Strategies that address stigmatizing attitudes toward people who use drugs and harm reduction may also facilitate naloxone expansion efforts, overall, as well as policies that improve the affordability and awareness of naloxone through the pharmacy.
A controlled evaluation of the effect of social prescribing programs on loneliness for adults in Queensland, Australia (protocol)
Authors: Dingle G. A. , Sharman L. S. , Hayes S. , Chua D. , Baker J. R. , Haslam C. , Jetten J. , Haslam S. A. , Cruwys T. , McNamara N. 
Published: July 2022

Abstract
Background
In social prescribing, link workers support individuals whose persistent health problems are exacerbated by loneliness by connecting them to community-based social activities. This approach is well established in the UK and is gaining attention in Australia. However, a major limitation of research to date has been a lack of theoretically informed and rigorous evaluations of social prescribing. We will address these points in this study, applying a social identity framework to examine the effects of group-based social prescribing (SP) activity compared to primary care treatment as usual (TAU).

Methods
Ninety participants experiencing loneliness recruited from primary care services and community centres across five sites in Southeast Queensland will be assigned to one of two conditions (SP, TAU) and assessed at two timepoints (baseline, + 8 weeks). Individuals will be aged 18 years and over, have sufficient English language skills to provide consent, and at the time of recruitment they will not be experiencing acute symptoms or social issues that require urgent intervention. Primary outcomes are loneliness, mental well-being, and health service use (total number of GP, hospital, and allied health visits in the past 3 months). Secondary outcomes will assess social group processes, including number of important social groups, new group identification, multiple identity compatibility, and group-based support and emotion regulation.

Discussion
This study will provide comprehensive data about the extent to which, and how, social prescribing to community-based group activities may help people to feel less lonely, more socially integrated, and healthy over the first 8 weeks. If effective, this social identity-informed model of social prescribing can be disseminated in communities across Australia.

Trial registration
ANZCTR, Registered 8 June 2022 - Retrospectively registered, https://www.anzctr.org.au/ACTRN12622000801718.aspx
Estimating the effects of policies on infertility prevalence worldwide
Authors: Zhang Xiaochen , Guan Quanquan , Yu Qiurun , Xiao Wenwen , Chen Ziyu , Dong Chao , Deng Siting , Zhuang Yin , Xia Yankai 
Published: July 2022

Abstract
Background
Infertility has troubled millions of people worldwide while always being an ignored issue. The high cost of treatment or lack of services placed a barrier to the alleviation of infertility status. Governments play a significant role to promote infertility-related policies for better access to infertility services and comprehensive supports for infertile people.

Methods
Data of infertility status indicators and infertility-related policies in ten representative countries were collected. An infertility-related policy system was established, then classification and quantification were processed according to specific criteria, and different policy implementation patterns were identified. The effectiveness of specific infertility-related policy and various patterns on infertility prevalence relief between 1990 and 2017 were evaluated via generalized linear models and analyses of covariance for the first time.

Results
Economic support policies would be less prioritized compared with social security policies, while economic support policy had a significant positive role in the decline of female infertility prevalence (β = -2·16, p = 0·042). In detail, insurance coverage and economic reward policies were crucial (β = -3·31, p = 0·031; β = -4·10, p = 0·025) with adjusted with covariates. The effect of economic support-oriented pattern was relatively better than other patterns for both male and female infertility prevalence relief. Nevertheless, the effectiveness of gradual-promotion pattern seemed preferable for male infertility prevalence relief while was similar with simultaneous-promotion pattern for females.

Conclusions
Our data-driven analysis revealed that insurance coverage and economic reward policies played the pivotal role in moderation of female infertility status. Economic support-oriented pattern and gradual-promotion pattern were preferable when promoting infertility-related policies.
Stelara struck: a case of noninfectious pneumonitis secondary to ustekinumab
Authors: Despotes Katherine A. , Vigeland Christine L. 
Published: July 2022

Abstract
Background
We describe a case of acute hypoxic respiratory failure due to drug induced lung disease secondary to ustekinumab, which is a monoclonal antibody used to treat psoriasis, psoriatic arthritis, and inflammatory bowel disease.

Case presentation
A 33-year-old man with a history of Crohn’s disease presented with fevers, myalgias, and abdominal pain, and subsequently developed acute hypoxemic respiratory failure approximately 2 weeks after restarting ustekinumab for his Crohn’s disease. Cross-sectional chest imaging showed ground glass opacities and bilateral consolidations. Due to progressive hypoxia, he ultimately required intubation and mechanical ventilation. Broad infectious and autoimmune work up was negative, making drug induced interstitial lung disease (DILD) the leading consideration. He was treated with high dose steroids with dramatic improvement in his respiratory status. At follow up, his imaging findings had largely resolved, and his pulmonary function tests were normal.

Conclusions
For patients presenting with acute hypoxic respiratory failure, it is critical to identify the underlying cause. In addition to testing for common respiratory infections that can cause respiratory failure, patients should also be evaluated for risk factors for developing atypical or opportunistic infections as well as inflammatory pneumonitis. Due to receiving ustekinumab, our patient was both at risk for developing an opportunistic infection as well as DILD. Although rare, DILD is a recognized toxicity of ustekinumab. Ustekinumab can cause significant lung injury, as in our patient, but with steroids and avoidance of future doses of the medication, our patient demonstrated good recovery. Reassuring outcomes have similarly been described in the literature; however, this case provides further details about outcomes with long-term follow-up clinical, imaging, and pulmonary function testing data available. We recommend consideration of high dose steroids for these patients for whom DILD is suspected.
Ectopic ACTH-producing neuroendocrine tumor occurring with large recurrent metastatic pheochromocytoma: a case report
Authors: Saishouji Fumi , Maeda Sarie , Hamada Hideaki , Kimura Noriko , Tamanoi Ai , Nishida Saiko , Sakaguchi Masaji , Igata Motoyuki , Yokoo Kiho , Kawakami Fumi , Araki Eiichi , Kondo Tatsuya 
Published: July 2022

Abstract
Background
Ectopic ACTH-dependent Cushing syndrome is rarely caused by pheochromocytoma (PCC). Glucocorticoid-regulated positive feedback loops in ACTH and catecholamines were proposed in some similar cases.

Case presentation
We present here an 80-year-old man who had previously undergone surgery for a left adrenal PCC and newly developed severe hypertension, hypokalemia, and typical Cushingoid manifestations. Investigations revealed hyperglycemia, hypokalemia, and extremely high catecholamines and their metabolites, ACTH and cortisol. Imaging modalities showed a recurrent large left adrenal mass positively visualized with 123I-metaiodobenzylguanidine as well as somatostatin receptor scintigraphy. Surgical interventions were not indicated; thus, metyrapone, phentolamine, and doxazocin were initiated, which successfully controlled his symptoms and biochemical conditions. With the evidence that metyrapone administration decreased ACTH and catecholamine levels, the existence of positive feedback loops was speculated. During the terminal stages of the disease, additional metyrosine treatment successfully stabilized his physiological and biochemical conditions. Upon the patient’s death, pathological autopsy was performed. Immunohistochemical analysis indicated that the tumor appeared to be co-positive with tyrosine hydroxylase (TH) as well as ACTH in most tumor cells in both PCC and liver metastasis. Most cells were clearly positive for somatostatin receptor 2 staining in the membrane compartment. The dense immunostaining of ACTH, TH, dopamine-β-hydroxylase and the large tumor size with positive feedback loops may be correlated with high levels of ACTH and catecholamines in the circulation.

Conclusions
We experienced a case of severe ectopic ACTH producing the largest reported recurrent malignant left PCC with liver metastases that presented positive feedback loops in the ACTH/cortisol and catecholamine/cortisol axes. Clinicians should be aware of the paradoxical response of ACTH on metyrapone treatment and possible steroid-induced catecholamine crisis.
Interoceptive accuracy is related to the psychological mechanisms of the burning mouth syndrome: a cross-sectional study
Authors: Yoshino Atsuo , Otsuru Naofumi , Doi Mitsuru , Maekawa Toru , Sasaoka Takafumi , Yamawaki Shigeto 
Published: July 2022

Abstract
Background
Different perspectives are needed to understand the pathophysiology of burning mouth syndrome (BMS), including physiological and psychological standpoints. The significance of interoception in chronic pain has been suggested. However, few studies have investigated this relationship in BMS. Therefore, we examined the role of interoception in BMS.

Methods
This is a cross-sectional study. BMS patients (N = 64) participated in the study. We used interoceptive accuracy (IAc) based on the heartbeat counting task. Then, participants were divided into high and low IAc groups, and their scores on clinical assessment including pain and psychological evaluation were compared.

Results
The Visual Analogue Scale scores indicating pain in low IAc patients, but not high IAc patients, were positively correlated with the Beck Depression Inventory-Second Edition (BDI-II) and the State-Trait Anxiety Inventory-State (STAI-S) Scores.

Conclusions
Interoception might play a role in the pathophysiology of BMS.