bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fluctuations in local and widespread mechanical sensitivity throughout the migraine cycle: a prospective longitudinal study
Authors: Scholten-Peeters Gwendolyne G. M. , Coppieters Michel W. , Durge Tom S. C. , Castien René F. 
Published: February 2020

Abstract
Background
People with migraine have localised (i.e., cephalic) mechanical sensitivity. There is uncertainty regarding widespread (i.e., extra-cephalic) mechanical sensitivity and variations in mechanical sensitivity throughout the migraine cycle. Therefore, this study aimed (1) to comprehensively assess mechanical sensitivity in both cephalic and extra-cephalic regions during the preictal, ictal, postictal and interictal phases; and (2) to compare these findings with mechanical sensitivity at corresponding time-points and locations in healthy participants.

Methods
According to sample size calculations, 19 people with migraine and 19 matched healthy volunteers participated in a prospective longitudinal study. Pressure pain thresholds were evaluated in three cephalic regions (temporalis, upper trapezius and C1 paraspinal muscles) and two extra-cephalic regions (extensor carpi radialis and tibialis anterior muscle) with a digital algometer during the four phases of the migraine cycle in people with migraine and at corresponding intervals and locations in healthy participants. Linear mixed model analyses with a random intercept were used.

Results
People with migraine had increased mechanical sensitivity in cephalic and extra-cephalic regions in all phases of the migraine cycle compared to healthy participants. Furthermore, this mechanical sensitivity was more severe in the preictal, ictal and postictal phase compared to the interictal phase in cephalic and extra-cephalic regions.

Conclusion
People with migraine have localised as well as widespread mechanical sensitivity compared to healthy participants. This sensitivity is even more pronounced immediately before, during and after a migraine attack.
QUality improvement in primary care to prevent hospitalisations and improve Effectiveness and efficiency of care for people Living with coronary heart disease (QUEL): protocol for a 24-month cluster randomised controlled trial in primary care
Authors: Redfern Julie , Hafiz Nashid , Hyun Karice , Knight Andrew , Hespe Charlotte , Chow Clara K. , Briffa Tom , Gallagher Robyn , Reid Christopher , Hare David L. , Zwar Nicholas , Woodward Mark , Jan Stephen , Atkins Emily R. , Laba Tracey-Lea , Halcomb Elizabeth , Billot Laurent , Johnson Tracey , Usherwood Timothy 
Published: February 2020

AbstractBackgroundCardiovascular disease (CVD), including coronary heart disease (CHD) and stroke, is the leading cause of death and disability globally. A large proportion of mortality occurs in people with prior CHD and effective and scalable strategies are needed to prevent associated deaths and hospitalisations. The aim of this study is to determine if a practice-level collaborative quality improvement program, focused on patients with CHD, reduces the rate of unplanned CVD hospitalisations and major adverse cardiovascular events, and increases the proportion of patients achieving risk factor targets at 24 months.MethodsCluster randomised controlled trial (cRCT) to evaluate the effectiveness of a primary care quality improvement program in 50 primary care practices (n~ 10,000 patients) with 24-month follow-up. Eligible practices will be randomised (1:1) to participate in either the intervention (collaborative quality improvement program) or control (standard care) regimens. Outcomes will be assessed based on randomised allocation, according to intention-to-treat. The primary outcome is the proportion of patients with unplanned CVD hospitalisations at 2 years. Secondary outcomes are proportion of patients with major adverse cardiovascular events, proportion of patients who received prescriptions for guideline-recommended medicines, proportion of patients achieving national risk factor targets and proportion with a chronic disease management plan or review. Differences in the proportion of patients who are hospitalised (as well as binary secondary outcomes) will be analysed using log-binomial regression or robust Poisson regression, if necessary.DiscussionDespite extensive research with surrogate outcomes, to the authors’ knowledge, this is the first randomised controlled trial to evaluate the effectiveness of a data-driven collaborative quality improvement intervention on hospitalisations, CVD events and cardiovascular risk amongst patients with CHD in the primary care setting. The use of data linkage for collection of outcomes will enable evaluation of this potentially efficient strategy for improving management of risk and outcomes for people with heart disease.Trial registrationAustralian New Zealand Clinical Trials Registry (ANZCTR) numberACTRN12619001790134(dated 20th December 2019).
Gastric schwannoma with giant ulcer and lymphadenopathy mimicking gastric cancer: a case report
Authors: Tang Caihua , Pan Qiyong , Xu Zeqing , Zhou Xuan , Wang Ying 
Published: February 2020

Abstract
Background
Gastric schwannomas are rare benign tumors originating from the intramuscular plexus of the stomach and account for just 2.6% of gastric mesenchymal tumors. Gastric schwannoma (GS) with a surface ulcer is very rare. Herein, we report a rare case of an ulcer-bearing GS, which in conjunction with multiple enlarged regional lymph nodes, readily mimicked gastric cancer (GC).

Case presentation
A 79-year-old female presented with poor appetite and intermittent vomiting of gastric contents during the past month. Gastroscopy revealed a giant crateriform ulcer within the stomach body (at the angular notch). Its raised and indurated border was fragile and bled easily. GC was thus suspected. Contrast-enhanced computer tomography (CT) revealed a mild enhancement of the corresponding irregularly thickened gastric wall, and an annular zone of mucosal discontinuity. Enlarged regional lymph nodes were also found, making GC with metastases of lymph nodes our primary concern. 18F-fluorodeoxyglueose position emission tomography (18F-FDG PET)/CT was then performed for further staging. Obviously increased FDG uptake was shown in the gastric lesion ((maximum standardized uptake value (SUVmax) 14.6), but no FDG uptake was observed in the enlarged regional lymph nodes. Given the strong suspicion of GC, subtotal gastrectomy was performed. GS was revealed by postoperative pathology, with no evidence of metastasis in the 13 resected lymph nodes.

Conclusions
This was a rare case of GS with a giant surface ulcer and multiple enlarged regional lymph nodes. The uptake of 18F-FDG in the tumor was substantially higher than previously published literature reports. Under these circumstances, it is difficult to be differentiated from GC.
The diagnosis “failure to thrive” and its impact on the care of hospitalized older adults: a matched case-control study
Authors: Tsui Clara , Kim Kristine , Spencer Martha 
Published: February 2020

Abstract
Background
“Failure to thrive” and associated diagnoses are non-specific terms applied to older adults when there is lack of diagnostic clarity and imply an absence of medical acuity. We investigated the effect of such admission diagnoses on delivery of patient care in a cohort of older adults admitted to a tertiary care teaching hospital.

Methods
Retrospective matched cohort study conducted at a tertiary care hospital in Vancouver, BC. Cases identified were adults aged ≥65 years admitted to acute medical wards with an admission diagnosis of “failure to thrive”, “FTT”, “failure to cope”, or “FTC”, between January 1, 2016 and November 1, 2017 (n = 60, median age 80 years). Age-matched controls met the same inclusion criteria with admission diagnoses other than those of interest (n = 60, median age 79 years).

Results
The primary outcome was time to admission, measured from time points in the emergency room that spanned from triage to completion of admission orders. Secondary outcomes were concordance of admission and discharge diagnoses and length of stay in hospital.
The total time from triage to admission for older adults admitted with FTT and associated diagnoses was 10 h 40 min, compared to 6 h 58 min for controls (p = .02). Concordance of admission and discharge diagnoses was only 12% for the “failure to thrive” cohort, and 95% for controls. Notably, 88% of the “failure to thrive” cohort had an acute medical diagnosis at the time of discharge. Patients in this cohort stayed 18.3 days in hospital compared to 10.2 days (p = .001).

Conclusions
Patients with an admission diagnosis of FTT or other associated diagnoses had significant delays in care when presenting to the emergency room, despite often having acute medical conditions on presentation. The use of this non-specific label can lead to premature diagnostic closure and should be avoided in clinical practice.
Comorbidities associated with HPV infection among people living with HIV-1 in the southeastern US: a retrospective clinical cohort study
Authors: Ye Yuanfan , Burkholder Greer A. , Wiener Howard W. , Griffin Russell , Aslibekyan Stella , Fry Karen , Khan Ashraf , Shrestha Sadeep 
Published: February 2020

Abstract
Background
The southeastern US is an epicenter for incident HIV in the US with high prevalence of human papillomavirus (HPV) co-infections. However, epidemiologies of HPV-associated clinical conditions (CC) among people living with HIV-1 infection (PLWH) are not fully known.

Methods
Electronic medical records (EMR) of PLWH attending one of the leading HIV clinics in the southeastern US between 2006 and 2018 were reviewed and analyzed. The retrospective study was nested within the University of Alabama at Birmingham HIV clinical cohort, which has electronically collected over 7000 PLWH’s clinical and sociobehavioral data since 1999. Incidence rates of HPV-related CC including anogenital warts, penile, anal, cervical, and vaginal/vulvar low- and high-grade squamous intraepithelial lesions (LSIL and HSIL) were estimated per 10,000 person years. Joinpoint regressions were performed to examine temporal changes in the trends of incident CC. All rates and trends were stratified by gender and race.

Results
Of the 4484 PLWH included in the study (3429 men, 1031 women, and 24 transgender), we observed 1038 patients with HPV-related CC. The median nadir CD4 count (cells/uL) was higher in the HPV-condition free group than the case groups (P < 0.0001). Anogenital warts, anal LSIL, HSIL, and cancer were more likely to be diagnosed among HIV-infected men than women. White men presented more frequently with anal LSIL and anal and penile cancers than black men (P < 0.03). White women were also more likely to be diagnosed with cervical HSIL (P = 0.023) and cancer (P = 0.037) than black women.

Conclusions
There were significant differences between gender and race with incidence of HPV-related CC among HIV patients. EMR-based studies provide insights on understudied HPV-related anogenital conditions in PLWH; however, large-scale studies in other regions are needed to generalize current findings and draw public health attention to co-infection induced non-AIDS defining comorbidities among PLWH.
Fatal acute Chagas disease by Trypanosoma cruzi DTU TcI, Ecuador
Authors: Calvopina Manuel , Segovia Gabriela , Cevallos William , Vicuña Yosselin , Costales Jaime A. , Guevara Angel 
Published: February 2020

Abstract
Background
Chagas disease is caused by the haemoflagellate protozoan Trypanosoma cruzi. Currently, T. cruzi recognizes seven discrete typing units (DTUs): TcI to TcVI and Tcbat. The genetic diversity of T. cruzi is suspected to influence the clinical outcome. Acute clinical manifestations, which include myocarditis and meningoencephalitis, are sometimes fatal; occur most frequently in children and in immunocompromised individuals. Acute disease is often overlooked, leading to a poor prognosis.

Case presentation
A 38-year-old man from a subtropical area of the Andes mountains of Ecuador was hospitalized after 3 weeks of evolution with high fever, chills, an enlarged liver, spleen, and lymph nodes, as well as facial edema. ECG changes were also observed. T. cruzi was identified in blood smears, culture and amplification of DNA by PCR. Tests for anti-T. cruzi IgG and IgM and HIV were negative. Molecular typing by restriction fragment length polymorphism (PCR-RFLP) determined the parasite to DTU TcI. In the absence of a timely anti-T. cruzi medication, the patient died.

Conclusions
This is a case of severe pathogenicity and the virulence of a DTU TcI strain in an adult patient. The severe acute Chagas disease was probably overlooked due to limited awareness and its low incidence. Our findings suggest that T. cruzi DTU TcI strains circulating in Ecuador are capable of causing fatal acute disease. Early diagnosis and prompt treatment is of paramount importance to avoid fatalities in acute infections.
Prevalence and mortality of cryptococcal disease in adults with advanced HIV in an urban tertiary hospital in Sierra Leone: a prospective study
Authors: Lakoh Sulaiman , Rickman Hannah , Sesay Momodu , Kenneh Sartie , Burke Rachael , Baldeh Mamadu , Jiba Darlinda F. , Tejan Yusuf S. , Boyle Sonia , Koroma Comfort , Deen Gibrilla F. , Beynon Fenella 
Published: February 2020

Abstract
Background
The global annual estimate for cryptococcal disease-related deaths exceeds 180,000, with three fourth occurring in sub-Saharan Africa. The World Health Organization (WHO) recommends cryptococcal antigen (CrAg) screening in all HIV patients with CD4 count < 100/μl. As there is no previous published study on the burden and impact of cryptococcal disease in Sierra Leone, research is needed to inform public health policies. We aimed to establish the seroprevalence and mortality of cryptococcal disease in adults with advanced HIV attending an urban tertiary hospital in Sierra Leone.

Methods
A prospective cohort study design was used to screen consecutive adult (18 years or older) HIV patients at Connaught Hospital in Freetown, Sierra Leone with CD4 count below 100 cells/mm3 from January to April 2018. Participants received a blood CrAg lateral flow assay (IMMY, Oklahoma, USA). All participants with a positive serum CrAg had lumbar puncture and cerebrospinal fluid (CSF) CrAg assay, and those with cryptococcal diseases had fluconazole monotherapy with 8 weeks followed up. Data were entered into Excel and analysed in Stata version 13.0. Proportions, median and interquartile ranges were used to summarise the data. Fisher’s exact test was used to compare categorical variables.

Results
A total of 170 patients, with median age of 36 (IQR 30–43) and median CD4 count of 45 cells/mm3 (IQR 23–63) were screened. At the time of enrolment, 54% were inpatients, 51% were newly diagnosed with HIV, and 56% were either ART-naïve or newly initiated (≤ 30 days). Eight participants had a positive blood CrAg, giving a prevalence of 4.7% (95% CI: 2.4–9.2%). Of those with a positive CrAg, CSF CrAg was positive in five (62.5%). Five (62.5%) CrAg-positive participants died within the first month, while the remaining three were alive and established on ART at 8 weeks.

Conclusion
A substantial prevalence of cryptococcal antigenaemia and poor outcome of cryptococcal disease were demonstrated in our study. The high mortality suggests a need for the HIV programme to formulate and implement policies on screening and pre-emptive fluconazole therapy for all adults with advanced HIV in Sierra Leone, and advocate for affordable access to effective antifungal therapies.
Salivary epigenetic biomarkers as predictors of emerging childhood obesity
Authors: Rushing Amanda , Sommer Evan C. , Zhao Shilin , Po’e Eli K. , Barkin Shari L. 
Published: February 2020

Abstract
Background
Epigenetics could facilitate greater understanding of disparities in the emergence of childhood obesity. While blood is a common tissue used in human epigenetic studies, saliva is a promising tissue. Our prior findings in non-obese preschool-aged Hispanic children identified 17 CpG dinucleotides for which differential methylation in saliva at baseline was associated with maternal obesity status. The current study investigated to what extent baseline DNA methylation in salivary samples in these 3–5-year-old Hispanic children predicted the incidence of childhood obesity in a 3-year prospective cohort.

Methods
We examined a subsample (n = 92) of Growing Right Onto Wellness (GROW) trial participants who were randomly selected at baseline, prior to randomization, based on maternal phenotype (obese or non-obese). Baseline saliva samples were collected using the Oragene DNA saliva kit. Objective data were collected on child height and weight at baseline and 36 months later. Methylation arrays were processed using standard protocol. Associations between child obesity at 36 months and baseline salivary methylation at the previously identified 17 CpG dinucleotides were evaluated using multivariable logistic regression models.

Results
Among the n = 75 children eligible for analysis, baseline methylation of Cg1307483 (NRF1) was significantly associated with emerging childhood obesity at 36-month follow-up (OR = 2.98, p = 0.04), after adjusting for child age, gender, child baseline BMI-Z, and adult baseline BMI. This translates to a model-estimated 48% chance of child obesity at 36-month follow-up for a child at the 75th percentile of NRF1 baseline methylation versus only a 30% chance of obesity for a similar child at the 25th percentile. Consistent with other studies, a higher baseline child BMI-Z during the preschool period was associated with the emergence of obesity 3 years later, but baseline methylation of NRF1 was associated with later obesity even after adjusting for child baseline BMI-Z.

Conclusions
Saliva offers a non-invasive means of DNA collection and epigenetic analysis. Our proof of principle study provides sound empirical evidence supporting DNA methylation in salivary tissue as a potential predictor of subsequent childhood obesity for Hispanic children. NFR1 could be a target for further exploration of obesity in this population.
Testicular expression of TDRD1, TDRD5, TDRD9 and TDRD12 in azoospermia
Authors: Babakhanzadeh Emad , Khodadadian Ali , Rostami Saadi , Alipourfard Iraj , Aghaei Mohsen , Nazari Majid , Hosseinnia Mehdi , Mehrjardi Mohammad Yahya Vahidi , Jamshidi Yalda , Ghasemi Nasrin 
Published: February 2020

Abstract
Background
Tudor domain-containing proteins (TDRDs) play a critical role in piRNA biogenesis and germ cell development. piRNAs, small regulatory RNAs, act by silencing of transposons during germline development and it has recently been shown in animal model studies that defects in TDRD genes can lead to sterility in males.

Methods
Here we evaluate gene and protein expression levels of four key TDRDs (TDRD1, TDRD5, TDRD9 and TDRD12) in testicular biopsy samples obtained from men with obstructive azoospermia (OA, n = 29), as controls, and various types of non-obstructive azoospermia containing hypospermatogenesis (HP, 28), maturation arrest (MA, n = 30), and Sertoli cell-only syndrome (SCOS, n = 32) as cases. One-way ANOVA test followed by Dunnett’s multiple comparison post-test was used to determine inter-group differences in TDRD gene expression among cases and controls.

Results
The results showed very low expression of TDRD genes in SCOS specimens. Also, the expression of TDRD1 and TDRD9 genes were lower in MA samples compared to OA samples. The expression of TDRD5 significantly reduced in SCOS, MA and HP specimens than the OA specimens. Indeed, TDRD12 exhibited a very low expression in HP specimens in comparison to OA specimens. All these results were confirmed by Western blot technique.

Conclusion
TDRDs could be very important in male infertility, which should be express in certain stages of spermatogenesis.
Immunogenomic pathways associated with cytotoxic lymphocyte infiltration and survival in colorectal cancer
Authors: Shen Yuanyuan , Guan Yue , Hummel Justin J. , Shyu Chi-Ren , Mitchem Jonathan B. 
Published: February 2020

Abstract
Background
Colorectal cancer (CRC) is the second leading cancer killer in the US today and patients with metastatic disease have only a 14% 5-year survival. One of the most impactful recent advances in cancer therapy, immune checkpoint inhibition, has not been shown to be effective for the majority of these patients. In this study, we use The Cancer Genome Atlas (TCGA) and recently developed informatic-based tools to identify targets for immune based therapy in colorectal cancer patients.

Methods
Open access, pre-processed (level 3) mRNA data and clinical data from colorectal patients from the TCGA was downloaded from FireCloud. Using the Microenvironment Cell Populations-Counter method (MCP-Counter), cytotoxic lymphocyte scores were calculated for all patients. Patients were then grouped by cytotoxic lymphocyte score (High vs Low), pathologic stage, and location to identify differentially expressed genes. Pathway enrichment analysis was performed using Reactome to determine differentially expressed genes associated with immune pathways. Survival analysis was performed with identified differentially expressed genes.

Results
In the TCGA dataset, there are 461 colon and 172 rectal cancer patients. After stratifying patients by cytotoxic lymphocyte score, anatomical location, and stage, we found a significant number of differentially expressed genes. We identified one pathway, “immunoregulatory interactions between a lymphoid and non-lymphoid cell”, that was highly enriched and included in all tumor locations and stages. Survival analysis performed with differentially expressed genes in this pathway identified 21 different genes associated with survival and cytotoxic lymphocyte infiltration, with ~ 70% of these genes occurring in the metastatic right-sided CRC group. Specifically, all genes associated with survival in the metastatic right-sided colorectal cancer group with low cytotoxic lymphocyte scores positively impacted survival.

Conclusions
Utilizing the TCGA, a publicly available dataset, and informatics-based analyses, we identified potential targets to improve immune based therapy in colorectal cancer. Additionally, we note the most targets in metastatic right-sided CRC patients, the patient group with the worst predicted survival. The results from this study demonstrate the ability of informatics-based analytic techniques to identify new therapeutic targets as well as improve patient selection for intervention, helping us to achieve the goals of precision-based oncology.