bluuebunny/crossref_metadata_2025_split huggingface dataset:
A prospective observational study exploring the association of comorbid chronic health conditions with total healthcare expenditure in people with mental health conditions in an Asian setting
Authors: Tyagi Shilpa , Ganesan Ganga , Subramaniam Mythily , Abdin Edimansyah , Vaingankar Janhavi Ajit , Chua Boon Yiang , Chong Siow Ann , Tan Kelvin Bryan 
Published: March 2022

AbstractBackgroundIt is pertinent to focus on chronic medical condition (CMC) comorbidity with mental health conditions (MHC) as their co-occurrence has significant cost and health implications. However, current evidence on co-occurrence of MHC with CMC is mixed and mostly from Western settings. Therefore, our study aimed to (i) describe the association between MHC and total healthcare expenditure, (ii) examine the association between CMC and total healthcare expenditure and (iii) examine determinants of total and different types of healthcare expenditure in respondents with and without MHC in an Asian setting.MethodsThe data from Singapore Mental Health Study (SMHS) 2016, a nationwide epidemiological survey, were linked with the National claims record (from 2017 to 2019). Multivariable Generalized Linear Models (GLM) were used to examine the association between MHC and total and different types of healthcare expenditure.ResultsA total of 3077 survey respondents were included in current analysis. Respondents with MHC had a lower mean age of 38.6 years as compared to those without MHC (47.1 years). MHC was associated with increased total healthcare expenditure after adjusting for covariates (b = 0.508,p < 0.05). In respondents with MHC, presence of CMC increased the total healthcare expenditure by 35% as compared to 40% increase in those without MHC. Interestingly, 35–49 years age group with MHC had almost 3 times higher total healthcare expenditure and 7.5 times higher inpatient expenditure as compared to the 18–34 years age group.ConclusionOur study highlights variations in association of CMC and age with total healthcare expenditure in those with versus without MHC in an Asian setting. Practical recommendations include appropriate planning and resource allocation for early diagnosis and management of MHC, proactive screening for CMC in those with MHC and addressing the dual issues of treatment gap and stigma to facilitate early help seeking and prevent episodic, costly healthcare utilization.
Prevalence of lifetime self-injurious thoughts and behaviors in a global sample of 599 patients reporting prospectively confirmed diagnosis with premenstrual dysphoric disorder
Authors: Eisenlohr-Moul Tory , Divine Madeline , Schmalenberger Katja , Murphy Laura , Buchert Brett , Wagner-Schuman Melissa , Kania Alyssa , Raja Sabina , Miller Adam Bryant , Barone Jordan , Ross Jaclyn 
Published: March 2022

AbstractBackgroundSuicide is the second leading cause of death among Americans ages 10 to 34, with alarming recent increases in suicide rates among those assigned female at birth. A large body of evidence points to menstrual cycle influences on self-injurious thoughts and behaviors (STBs), suggesting that neurobiological hormone sensitivities, such as in premenstrual dysphoric disorder (PMDD), may drive suicide risk in females. However, existing studies of STBs in PMDD use cross-sectional self-report measures of PMDD with poor validity. As a first step to establish accurate prevalence rates of STBs in PMDD, we examined the lifetime prevalence of STBs in a large global survey of patients reporting a diagnosis of PMDD based on daily ratings.MethodIndividuals with self-reported PMDD symptoms were invited to an online survey through online support groups for PMDD and social media posts from PMDD awareness accounts. Participants reported demographics, whether they had been diagnosed with PMDD by a healthcare provider using daily ratings, STBs using the Columbia Suicide Severity Rating Scale, and history of lifetime comorbid psychiatric diagnoses.ResultsOf 2,689 survey completers, 599 (23%) reported a diagnosis with PMDD based on two months of daily ratings and were included in analyses. We observed high rates of lifetime active suicidal ideation (72%), planning (49%), intent (42%), preparing for an attempt (40%), and attempt (34%), as well as non-suicidal self-injury (51%). The majority (70%) of the sample reported at least one lifetime comorbid psychiatric diagnosis. Predictors of lifetime active suicidal ideation included nulliparity, low-to-moderate (vs. high) income, and history of diagnosis with major depression or post-traumatic stress disorder. Predictors of lifetime attempts among those reporting lifetime active ideation included older age, nulliparity, lower income, and history of diagnosis with post-traumatic stress disorder or borderline personality disorder.ConclusionsThese data indicate high rates of STBs among those reporting prospective diagnosis of PMDD and highlight the need for prospective research on mechanisms and prevention of STBs in PMDD. Clinical practice guidelines for PMDD should accommodate comorbidities and recommend frequent screenings for STB risk. STBs should be considered for inclusion in future iterations of the DSM PMDD diagnostic criteria.
Association between weather and utilisation of physical therapy in patients with osteoarthritis: a case-crossover study
Authors: Wu Ruo-Yan , Pan Ren-Hao , Wu Chiung-Yi , Chan Chien-Lung , Yeh Huan-Jui 
Published: March 2022

Abstract
Background
During varied weather conditions, patients with osteoarthritis experience different severity of symptoms and signs. However, weather may also cause barriers or incentives for patients to seek medical services. These factors may result in changes in medical utilisation; however, no studies have investigated whether the probability of physical therapy utilisation among patients with osteoarthritis is associated with changes in meteorological factors.

Method
By using a secondary data of NHID in Taiwan, we conducted a population-based, retrospective study with case-crossover design for patients initially diagnosed with osteoarthritis between 2000 and 2013. The meteorological factors of months with the lowest treatment rate were used as patients’ own control periods and compared with the parameters of months with high treatment frequency. The risk of exposure to different meteorological factors, including mean temperature, daily highest temperature, daily minimum temperature, diurnal temperature range, relative humidity, and barometric pressure, was estimated and represented by odds ratios (ORs) and 95% confidence intervals (CIs).

Results
A total of 8,130 patients were recruited. Regardless of univariate or multivariable analysis, increased daily highest temperature enhanced the frequency of physical therapy (OR: 1.04; 95% CI: 1.02–1.05; p < 0.01; OR: 1.07; 95% CI: 1.04–1.10; p < 0.01). When the weather was hotter (> 23 °C), higher diurnal temperature range and humidity resulted in an increase in the utilisation of physical therapy. However, when the weather was colder (< 23 °C), reverse effects were observed.

Conclusions
An increase in temperature increases the probability of physical therapy resource use. Therefore, temperature, along with other meteorological factors, may play a key role in the utilization of physical therapy among patients with osteoarthritis.
Interplay between bladder microbiota and overactive bladder symptom severity: a cross‐sectional study
Authors: Li Kun , Chen Chunxiao , Zeng Jiarong , Wen Yuehui , Chen Weihong , Zhao Jie , Wu Peng 
Published: March 2022

Abstract
Background
It is widely accepted that there exist microbiota communities in urinary tract of healthy individuals. Imbalance in the urinary microbiome plays important roles in the development of various benign urological conditions including lower urinary track symptoms (LUTS) and overactive bladder (OAB). However, whether alteration in urinary microbiome exerts influence on the severity of OAB symptom has yet to be elucidated. The purpose of this study is to examine the correlation between urinary microbiome and the severity of OAB.

Methods
A total of 70 OAB patients were recruited to finish overactive bladder symptom score (OABSS) questionnaires. Catheterized urine samples were obtained for 16S rRNA gene sequencing. The species richness and evenness were evaluated by α diversity, and the difference in urinary microbiome between patients with mild or moderate/severe severity was evaluated by β diversity. The relationship between urinary microbiome and the severity of OAB symptom was evaluated using Pearson’s correlation analysis.

Results
Mild patients (OABSS ≤ 5, n = 17) had lower bacterial diversity (Simpson index, P = 0.024) and richness (Chao1, P = 0.023) than those with moderate/severe symptom (OABSS > 5, n = 53). Beta-diversity of urinary microbiome between two groups were significantly different. Furthermore, the score of OABSS was positively correlated with the richness index (Chao1, P = 0.002) and diversity index (Shannon index, P = 0.044) of urinary microbiome. Certain bacterial genera (e.g., Porphyromona and Prevotella) were significantly correlated with severity of OAB sub-symptoms.

Conclusion
This study demonstrated that urinary microbiome was intimately correlated with the severity of OAB symptom and the increase of the diversity and richness of urinary microbiome was accompanied by more severe OAB symptoms, indicating that urinary dysbiosis may play pivotal roles in the deterioration of functional bladder diseases.
Single-cell sequencing reveals MYC targeting gene MAD2L1 is associated with prostate cancer bone metastasis tumor dormancy
Authors: Wang Xing , Yu Jiandi , Yan Junfeng , Peng Kun , Zhou Haiyong 
Published: March 2022

Abstract
Background
Among malignant tumors, bone metastasis is frequently associated with prostate cancer which is seen in about 80% of patients. During cancer treatments, some tumor cells switch to a "dormant mode" to help tumor cells avoid attack from the immune system and anti-tumor therapies. In this dormant mode, tumor cells can be resuscitated, causing cancer to reoccur. The generally accepted explanation for this phenomenon is that the tumor cells have spread to the bone marrow before treatment and are dormant in the bone marrow. However, the key mechanism for inducing and maintaining the dormancy of these prostate cancer disseminated tumor cells in the bone marrow is still unclear. Therefore, studying the dormancy mechanism of tumor cells in bone metastasis is of great significance for the treatment and the prevention of recurrence of prostate cancer.

Methods
We obtained single-cell RNA-seq data of tumors from mouse models of prostate cancer bone metastasis mouse model numbered (GSE147150) from the GEO database, and obtained RNA-seq expression data and clinical information from The Cancer Genome Atlas Program (TCGA) of prostate cancer patients from the USCS Xena database. Screening of differential genes and annotation of GO functions were performed separately. Subsequently, the screened differential genes were compared and analyzed with 50 classic Hallmark signaling pathways, and the prognosis analysis of prostate cancer patients in TCGA data was performed to discover the key genes of the dormant mechanism of tumor cells in bone metastasis, and obtain new biomarkers that can be used to predict the prognosis of patients.

Results
A total of 378 differentially expressed genes were screened, of which 293 were significantly up-regulated and 85 were significantly down-regulated. Among them, the up-regulated genes were mainly related to the immune response, and the down-regulated genes were mainly related to the cell cycle. Through GSVA (Gene set variation analysis), it is found that there are differences in a total of 3 signal pathways: COMPLEMENT, MYC_TARGETS_V1 and MYC_TARGETS_V2. By comparing and analyzing the significantly down-regulated genes in dormant tumor cells with MYC_TARGETS_V1, MYC_TARGETS_V2, three significantly down-regulated genes were obtained: Ccna2, Mad2L1 and Plk1.

Conclusion
In summary, our findings indicate that the MYC targeting gene Mad2L1 is potentially related to the dormancy mechanism of prostate cancer. At the same time, Mad2L1, a gene associated with dormant prostate cancer cells, may be used as a biomarker for prognostic survival.
Association of the angiotensin I converting enzyme (ACE) gene polymorphisms with recurrent aphthous stomatitis in the Czech population: case–control study
Authors: Bartakova Julie , Deissova Tereza , Slezakova Simona , Bartova Jirina , Petanova Jitka , Kuklinek Pavel , Fassmann Antonin , Borilova Linhartova Petra , Dušek Ladislav , Izakovicova Holla Lydie 
Published: March 2022

Abstract
Background
Recurrent aphthous stomatitis (RAS) is multifactorial disease with unclear etiopathogenesis. The aim of this study was to determine distribution of the angiotensin I converting enzyme (ACE) gene polymorphisms and their influence on RAS susceptibility in Czech population.

Methods
The study included 230 subjects (143 healthy controls and 87 patients with RAS) with anamnestic, clinical and laboratory data. Five ACE gene polymorphisms (rs4291/rs4305/rs4311/rs4331/rs1799752 = ACE I/D) were determined by TaqMan technique.

Results
The allele and genotype distributions of the studied ACE I/D polymorphisms were not significantly different between subjects with/without RAS (Pcorr > 0.05). However, carriers of II genotype were less frequent in the RAS group (OR = 0.48, 95% CI = 0.21–1.12, P = 0.059). Stratified analysis by sex demonstrated lower frequency of II genotype in women (OR = 0.33, 95% CI = 0.09–1.17, P < 0.035, Pcorr > 0.05, respectively) than in men with RAS (P > 0.05). Moreover, the frequency of AGTGD haplotype was significantly increased in RAS patients (OR = 13.74, 95% CI = 1.70–110.79, P = 0.0012, Pcorr < 0.05). In subanalysis, TGD haplotype was significantly more frequent in RAS patients (P < 0.00001) and CGI haplotype was less frequent in RAS patients (P < 0.01), especially in women (P = 0.016, Pcorr > 0.05).

Conclusions
Our study indicates that while the AGTGD and TGD haplotypes are associated with increased risk of RAS development, CGI haplotype might be one of protective factors against RAS susceptibility in Czech population.
Anti-glycation properties of Illicium verum Hook. f. fruit in-vitro and in a diabetic rat model
Authors: Khan Hafiz Nadeem , Rasheed Saima , Choudhary M. Iqbal , Ahmed Nessar , Adem Abdu 
Published: March 2022

Abstract
Background
Chronic hyperglycemic triggers the non-enzymatic glycation of biomolecules, resulting in the production of advanced glycation endproducts, that lead to several micro- and macrovascular complications. Therefore, the discovery of new, effective, and safe anti-glycation agents is an important need. One of the best choices for the management of diabetes is to use complementary and alternative medicinal therapies. Therefore, the present study was designed to evaluate the anti-glycation activity of ethanolic extract of Illicium verum Hook. f. (Star anise, a frequently used spice and medicinally important herb).

Methods
The anti-glycation activity of ethanolic extract of Illicium verum Hook. f. was determined by using both in-vitro and in-vivo assays. HSA-fructose glycation model was employed to assess the in-vitro inhibition of protein glycation, additionally cross-linked AGEs (formed by incubating lysozyme with fructose) were assessed by SDS polyacrylamide gel electrophoresis. Dual inhibitory mechanisms, i.e., antioxidant and metal chelating activities, were also evaluated by using DPPH, ABTS, and Fe (II)-chelation assays. Acute toxicity of I. verum extract was also performed (by administrating different doses i.e. 2,000, 1,500, 1,000, and 500 mg/kg of body weight). Finally, in-vivo anti-glycation potential was evaluated by 7 weeks of administration of I. verum extract in streptozotocin-induced diabetic rats.

Results
In HSA-fructose glycation model, extract of I. verum showed a good inhibitory activity with IC50 value of 0.11±0.001 mg/mL, as compared to the standard inhibitor, rutin (IC50 = 0.02±0.01 mg/mL). Extract of I. verum showed inhibitory activity in DPPH, and ABTS radical scavenging assays with IC50 values of 130±1.0, and 57±2.0 μg/mL, respectively, while it was found to be inactive in the Fe+2-chelation assay. The extract was found to be non-toxic, and reduce the elevated blood glucose, urea, lipid, liver function parameters, and renal AGEs levels in streptozotocin-induced diabetic rats.

Conclusions
These results suggest that I. verum supplementation might help to reduce the burden of AGEs, and may have potential in preventing diabetes-associated complications.
Hydro-ethanol extract of Holarrhena floribunda stem bark exhibits anti-anaphylactic and anti-oedematogenic effects in murine models of acute inflammation
Authors: Antwi Stephen , Oduro-Mensah Daniel , Obiri David Darko , Osafo Newman , Antwi Aaron Opoku , Ansah Helena Owusu , Ocloo Augustine , Okine Laud K. N.-A. 
Published: March 2022

AbstractBackgroundHolarrhena floribunda(G.Don) T.Durand & Schinz stem bark has anecdotal use in Ghanaian folk medicine for the management of inflammatory conditions. This study was conducted to investigate the in vivo anti-inflammatory activity of the bark extract using models of acute inflammation in male Sprague Dawley rats, C57BL/6 mice and ICR mice.MethodsA 70% hydro-ethanol extract of the stem bark (HFE) was evaluated at doses of 5–500 mg/kg bw. Local anaphylaxis was modelled by the pinnal cutaneous anaphylactic test. Systemic anaphylaxis or sepsis were modeled by compound 48/80 or lipopolysaccharide, respectively. Clonidine-induced catalepsy was used to investigate the effect on histamine signaling. Anti-oedematogenic effect was assessed by induction with carrageenan. Effects on mediators of biphasic acute inflammation were studied using histamine and serotonin (early phase) or prostaglandin E2 (late phase).ResultsHFE demonstrated anti-inflammatory and/or anti-oedematogenic activity comparable to standard doses of aspirin and diclofenac (inhibitors of cyclooxygenases-1 and -2), chlorpheniramine (histamine H1-receptor antagonist), dexamethasone (glucocorticoid receptor agonist), granisetron (serotonin receptor antagonist) and sodium cromoglycate (inhibitor of mast cell degranulation). All observed HFE bioactivities increased with dose.ConclusionsThe data provide evidence that the extract ofH. floribundastem bark has anti-anaphylactic and anti-oedematogenic effects; by interfering with signalling or metabolism of histamine, serotonin and prostaglandin E2which mediate the progression of inflammation. The anti-inflammatory and antihistaminic activities of HFE may be relevant in the context of the management of COVID-19.
Knockdown of RSPH14 inhibits proliferation, migration, and invasion and promotes apoptosis of hepatocellular carcinoma via RelA
Authors: Yuan Dawei , Ma Rulan , Sun Tuanhe , Zhu Kun , Dang Chengxue , Ye Haixia , Li Kang 
Published: March 2022

Abstract
Background
High RSPH14 expression appears to be related to poor prognosis of hepatocellular carcinoma (HCC). This study aimed to investigate the possible roles of RSPH14 in the proliferation, apoptosis, and invasion of HCC cells.

Methods
The UALCAN database and Kaplan–Meier Plotter were used to evaluate the expression level and prognostic role of RSPH14 in HCC. Lentiviral vectors containing shRNA against RSPH14 were constructed to transfect the BEL-7404 and SMMC-7721 HCC cell lines. Cell proliferation was investigated by BrdU, MTT, and colony-formation assays. Apoptosis was detected using flow cytometry. Cell migration and invasion were evaluated using the scratch wound-healing and Transwell assays. Immunohistochemistry and western blot were used to determine the expression levels of the proteins. The function of RSPH14 in vivo was evaluated using a xenograft mouse model.

Results
The expression of RSPH14 was higher in HCC tumor tissues than in adjacent normal tissues and was closely related to unfavorable prognostic factors and poorer survival (all P < 0.05). Knockdown of RSPH14 inhibited the cell proliferation, migration, and invasion of HCC cells and promoted apoptosis (all P < 0.05). Knockdown of RSPH14 inhibited tumor growth in vivo (P < 0.05). RSPH14 knockdown led to decreased expression of RelA (NF-κBp65), CDH2, and AKT1, thereby affecting the functions of the HCC cells (all P < 0.05). RelA overexpression could abate the inhibitory effect of BEL-7404 cell proliferation caused by RSPH14 depletion.

Conclusion
Knockdown of RSPH14 could decrease cell proliferation, migration, and invasion and increase apoptosis of HCC cells by inhibiting RelA expression. RSPH14 could be a new treatment target for HCC.
KRAS acting through ERK signaling stabilizes PD-L1 via inhibiting autophagy pathway in intrahepatic cholangiocarcinoma
Authors: Gao Zheng , Chen Jia-Feng , Li Xiao-Gang , Shi Ying-Hong , Tang Zheng , Liu Wei-Ren , Zhang Xin , Huang Ao , Luo Xuan-Ming , Gao Qiang , Shi Guo-Ming , Ke Ai-Wu , Zhou Jian , Fan Jia , Fu Xiu-Tao , Ding Zhen-Bin 
Published: March 2022

Abstract
Background
While the correlation between PD-L1 expression and KRAS mutation has been previously reported in other solid tumors such as non-small cell lung cancer (NSCLC), whether PD-L1 can be modulated by ERK signaling downstream of KRAS in intrahepatic cholangiocarcinoma (iCCA) and the underlying molecular regulatory mechanism remain unclear.

Methods
The expression of ERK, p-ERK, PD-L1 and autophagy markers following KRAS knockdown or Ras/Raf/MEK/ERK signaling inhibitors treatment was examined in two human iCCA cell lines (HuCCT1 and RBE) using western blotting and immunofluorescence. Both pharmacological autophagy inhibitors and short-interfering RNA against ATG7 were applied to inhibit autophagy. The apoptosis rates of iCCA cell lines were detected by flow cytometry and CCK-8 after co-culturing with CD3/CD28-activated human CD8+ T lymphocytes. Immunohistochemistry was applied to detect the correlation of ERK, p-ERK and PD-L1 in 92 iCCA tissues.

Results
The present study demonstrated that the PD-L1 expression level was distinctly reduced in KRAS-mutated iCCA cell lines when ERK signaling was inhibited and ERK phosphorylation levels were lowered. The positive association between p-ERK and PD-L1 was also verified in 92 iCCA tissue samples. Moreover, ERK inhibition induced autophagy activation. Both inhibiting autophagy via autophagy inhibitors and genetically silencing the ATG7 expression partially reversed the reduced PD-L1 expression caused by ERK inhibition. In addition, ERK-mediated down-regulation of PD-L1 via autophagy pathways induced the apoptosis of iCCA cells when co-cultured with CD3/CD28-activated human CD8+ T lymphocytes in vitro.

Conclusions
Our results suggest that ERK signaling inhibition contributes to the reduction of PD-L1 expression through the autophagy pathway in iCCA. As a supplement to anti-PD-1/PD-L1 immunotherapy, ERK-targeted therapy may serve as a potentially novel treatment strategy for human KRAS-mutated iCCA.