bluuebunny/crossref_metadata_2025_split huggingface dataset:
Systematic review of studies investigating ventilator associated pneumonia diagnostics in intensive care
Authors: Al-Omari Basem , McMeekin Peter , Allen A. Joy , Akram Ahsan R. , Graziadio Sara , Suklan Jana , Jones William S. , Lendrem B. Clare , Winter Amanda , Cullinan Milo , Gray Joanne , Dhaliwal Kevin , Walsh Timothy S. , Craven Thomas H. 
Published: June 2021

AbstractBackgroundVentilator-associated pneumonia (VAP) is an important diagnosis in critical care. VAP research is complicated by the lack of agreed diagnostic criteria and reference standard test criteria. Our aim was to review which reference standard tests are used to evaluate novel index tests for suspected VAP.MethodsWe conducted a comprehensive search using electronic databases and hand reference checks. The Cochrane Library, MEDLINE, CINHAL, EMBASE, and web of science were searched from 2008 until November 2018. All terms related to VAP diagnostics in the intensive treatment unit were used to conduct the search. We adopted a checklist from the critical appraisal skills programme checklist for diagnostic studies to assess the quality of the included studies.ResultsWe identified 2441 records, of which 178 were selected for full-text review. Following methodological examination and quality assessment, 44 studies were included in narrative data synthesis. Thirty-two (72.7%) studies utilised a sole microbiological reference standard; the remaining 12 studies utilised a composite reference standard, nine of which included a mandatory microbiological criterion. Histopathological criteria were optional in four studies but mandatory in none.ConclusionsNearly all reference standards for VAP used in diagnostic test research required some microbiological confirmation of infection, with BAL culture being the most common reference standard used.
A case of tamoxifen-induced hypertriglyceridemia monitoring the changes in lipoprotein fractions over time
Authors: Isobe Hayato , Shimoda Masashi , Kan Yuki , Tatsumi Fuminori , Katakura Yukino , Kimura Tomohiko , Obata Atsushi , Kohara Kenji , Nakanishi Shuhei , Mune Tomoatsu , Kaku Kohei , Kaneto Hideaki 
Published: June 2021

Abstract
Background
Tamoxifen, which is one of the selective estrogen receptor modulators (SERMs), can bring out life-threatening complication, e.g. hypertriglyceridemia-induced acute pancreatitis, although it is rare. We precisely report changes in lipoprotein metabolism before and after tamoxifen discontinuation because there have been few reports of it.

Case presentation
47-year-old premenopausal woman with dyslipidemia, type 2 diabetes, nonalcoholic fatty liver disease and chronic kidney disease was prescribed tamoxifen as adjuvant therapy after operation of breast cancer. She experienced severe tamoxifen-induced hypertriglyceridemia several months after dosing tamoxifen. Before cessation of tamoxifen, lipoprotein fraction test revealed marked stagnation of VLDL and IDL metabolisms, resulting in severe hypertriglyceridemia (serum triglyceride level was 1881 mg/dL). Seven days after tamoxifen withdrawal, lipoprotein fraction test showed that the metabolisms of endogenous lipoproteins were changed drastically.

Conclusions
From these results, we confirmed that tamoxifen certainly changes lipoprotein metabolism through suppression of post-heparin lipolytic activity. It is very important to evaluate the balance between benefit and risk before dosing tamoxifen and survey lipid profiles constantly during treatment to avoid life-threatening complication when prescription of tamoxifen is planned.
The societal cost and economic impact of surgical care on patients’ households in rural Uganda; a mixed method study
Authors: Nwanna–Nzewunwa Obieze , Oke Rasheedat , Agwang Esther , Ajiko Mary-Margaret , Yoon Christopher , Carvalho Melissa , Kirya Fred , Marseille Elliot , Dicker Rochelle A. 
Published: June 2021

Abstract
Background
The epidemiology and cost of surgical care delivery in low-and middle-income countries (LMICs) is poorly understood. This study characterizes the cost of surgical care, rate of catastrophic medical expenditure and medical impoverishment, and impact of surgical hospitalization on patients’ households at Soroti Regional Referral Hospital (SRRH), Uganda.

Methods
We prospectively collected demographic, clinical, and cost data from all surgical inpatients and caregivers at SRRH between February 2018 and January 2019. We conducted and thematically analyzed qualitative interviews to discern the impact of hospitalization on patients’ households. We employed the chi-square, t-test, ANOVA, and Bonferroni tests and built regression models to identify predictors of societal cost of surgical care. Out of pocket spending (OOPS) and catastrophic expenses were determined.

Results
We encountered 546 patients, mostly male (62%) peasant farmers (42%), at a median age of 22 years; and 615 caregivers, typically married (87%), female (69%), at a median age of 35 years. Femur fractures (20.4%), soft tissue infections (12.3%), and non-femur fractures (11.9%) were commonest. The total societal cost of surgical care was USD 147,378 with femur fractures (USD 47,879), intestinal obstruction (USD 18,737) and non-femur fractures (USD 10,212) as the leading contributors. Procedures (40%) and supplies (12%) were the largest components of societal cost. About 29% of patients suffered catastrophic expenses and 31% were medically impoverished.

Conclusion
Despite free care, surgical conditions cause catastrophic expenses and impoverishment in Uganda. Femur fracture is the most expensive surgical condition due to prolonged hospitalization associated with traction immobilization and lack of treatment modalities with shorter hospitalization.
Occurrence and potentially zoonotic genotypes of Enterocytozoon bieneusi in wild rhesus macaques (Macaca mulatta) living in Nanwan Monkey Island, Hainan, China: a public health concern
Authors: Zhao Wei , Zhou Huan-Huan , Ren Guang-Xu , Qiang Yu , Huang Hui-Cong , Lu Gang , Tan Feng 
Published: June 2021

AbstractBackgroundEnterocytozoon bieneusi, a microsporidian species, is a zoonotic pathogen found in both humans and animals. Here, we determined the prevalence, explored the different genotypes ofE. bieneusiin wild rhesus macaques (Macaca mulatta) (Hainan Island of China), and assessed their zoonotic potential.MethodsWe collected 173 fecal specimens from wild rhesus macaques living in Nanwan Monkey Island, Hainan, China. Subsequently, we identified and genotypedE. bieneusiusing nested PCR analysis amplification of the internal transcribed spacer region (ITS) of the rRNA gene. Lastly, a neighbor-joining tree was built based on gene sequences from the ITS region ofE.bieneusi.ResultsOf the 173 specimens from wild rhesus macaques, 26 (15%) were infected withE. bieneusi. We identified six genotypes ofE. bieneusi, of which five were known: PigEBITS7 (n = 20), D (n = 2), Type IV (n = 1), Peru6 (n = 1), Henan-III (n = 1), and a novel genotype: HNM-IX (n = 1). From the phylogenetic analysis, the six genotypes identified here were all clustered into zoonotic group 1.ConclusionThis study is the first report to detectE. bieneusiinfection in wild rhesus macaques from Hainan, China. Human-pathogenic genotypes D, Henan-III, Peru6, PigEbITS7, and Type IV in the wild rhesus macaques support these animals infected withE. bieneusihave a public health significance.
Overexpression of DDIT4 and TPTEP1 are associated with metastasis and advanced stages in colorectal cancer patients: a study utilizing bioinformatics prediction and experimental validation
Authors: Fattahi Fahimeh , Kiani Jafar , Alemrajabi Mahdi , Soroush Ahmadreza , Naseri Marzieh , Najafi Mohammad , Madjd Zahra 
Published: June 2021

Abstract
Background
Various diagnostic and prognostic tools exist in colorectal cancer (CRC) due to multiple genetic and epigenetic alterations causing the disease. Today, the expression of RNAs is being used as prognostic markers for cancer.

Methods
In the current study, various dysregulated RNAs in CRC were identified via bioinformatics prediction. Expression of several of these RNAs were measured by RT-qPCR in 48 tissues from CRC patients as well as in colorectal cancer stem cell-enriched spheroids derived from the HT-29 cell line. The relationships between the expression levels of these RNAs and clinicopathological features were analyzed.

Results
Our bioinformatics analysis determined 11 key mRNAs, 9 hub miRNAs, and 18 lncRNAs which among them 2 coding RNA genes including DDIT4 and SULF1 as well as 3 non-coding RNA genes including TPTEP1, miR-181d-5p, and miR-148b-3p were selected for the further investigations. Expression of DDIT4, TPTEP1, and miR-181d-5p showed significantly increased levels while SULF1 and miR-148b-3p showed decreased levels in CRC tissues compared to the adjacent normal tissues. Positive relationships between DDIT4, SULF1, and TPTEP1 expression and metastasis and advanced stages of CRC were observed. Additionally, our results showed significant correlations between expression of TPTEP1 with DDIT4 and SULF1.

Conclusions
Our findings demonstrated increased expression levels of DDIT4 and TPTEP1 in CRC were associated with more aggressive tumor behavior and more advanced stages of the disease. The positive correlations between TPTEP1 as non-coding RNA and both DDIT4 and SULF1 suggest a regulatory effect of TPTEP1 on these genes.
Care-seeking behaviour and socio-economic burden associated with uncomplicated malaria in the Democratic Republic of Congo
Authors: Kayiba Nadine Kalenda , Yobi Doudou Malekita , Devleesschauwer Brecht , Mvumbi Dieudonné Makaba , Kabututu Pius Zakayi , Likwela Joris Losimba , Kalindula Lydie Azama , DeMol Patrick , Hayette Marie-Pierre , Mvumbi Georges Lelo , Lusamba Paul Dikassa , Beutels Philippe , Rosas-Aguirre Angel , Speybroeck Niko 
Published: June 2021

AbstractBackgroundThis study aimed to estimate the socio-economic costs of uncomplicated malaria and to explore health care-seeking behaviours that are likely to influence these costs in the Democratic Republic of Congo (DRC), a country ranked worldwide as the second most affected by malaria.MethodsIn 2017, a cross-sectional survey included patients with uncomplicated malaria in 64 healthcare facilities from 10 sentinel sites of the National Malaria Control Programme (NMCP) in the DRC. A standard questionnaire was used to assess health care-seeking behaviours of patients. Health-related quality of life (HRQL) and disutility weights (DW) of illness were evaluated by using the EuroQol Group’s descriptive system (EQ-5D-3L) and its visual analogue scale (EQ VAS). Malaria costs were estimated from a patient’s perspective. Probabilistic sensitivity analyses (PSA) evaluated the uncertainty around the cost estimates. Generalized regression models were fitted to assess the effect of potential predictive factors on the time lost and the DW during illness.ResultsIn total, 1080 patients (age: 13.1 ± 14 years; M/F ratio: 1.1) were included. The average total costs amounted to US$ 36.3 [95% CI 35.5–37.2] per malaria episode, including US$ 16.7 [95% CI 16.3–17.1] as direct costs and US$ 19.6 [95% CI 18.9–20.3] indirect costs. During care seeking, economically active patients and their relatives lost respectively 3.3 ± 1.8 and 3.4 ± 2.1 working days. This time loss occurred mostly at the pre-hospital stage and was the parameter associated the most with the uncertainty around malaria cost estimates. Patients self-rated an average 0.36 ± 0.2 DW and an average 0.62 ± 0.3 EQ-5D index score per episode. A lack of health insurance coverage (896 out of 1080; 82.9%) incurred substantially higher costs, lower quality of life, and heavier DW while leading to longer time lost during illness. Residing in rural areas incurred a disproportionally higher socioeconomic burden of uncomplicated malaria with longer time lost due to illness and limited access to health insurance mechanisms.ConclusionUncomplicated malaria is associated with high economic costs of care in the DRC. Efforts to reduce the cost-of-illness should target time lost at the pre-hospital stage and social disparities in the population, while reinforcing measures for malaria control in the country.
MicroRNA-30a-5p promotes differentiation in neonatal mouse spermatogonial stem cells (SSCs)
Authors: Khanehzad Maryam , Nourashrafeddin Seyed Mehdi , Abolhassani Farid , Kazemzadeh Shokoofeh , Madadi Soheila , Shiri Elham , Khanlari Parastoo , Khosravizadeh Zahra , Hedayatpour Azim 
Published: June 2021

Abstract
Background
The importance of spermatogonial stem cells (SSCs) in spermatogenesis is crucial and intrinsic factors and extrinsic signals mediate fate decisions of SSCs. Among endogenous regulators, microRNAs (miRNAs) play critical role in spermatogenesis. However, the mechanisms which individual miRNAs regulate self- renewal and differentiation of SSCs are unknown. The aim of this study was to investigate effects of miRNA-30a-5p inhibitor on fate determinations of SSCs.

Methods
SSCs were isolated from testes of neonate mice (3–6 days old) and their purities were performed by flow cytometry with ID4 and Thy1 markers. Cultured cells were transfected with miRNA- 30a-5p inhibitor. Evaluation of the proliferation (GFRA1, PLZF and ID4) and differentiation (C-Kit & STRA8) markers of SSCs were accomplished by immunocytochemistry and western blot 48 h after transfection.

Results
Based on the results of flow cytometry with ID4 and Thy1 markers, percentage of purity of SSCs was about 84.3 and 97.4 % respectively. It was found that expression of differentiation markers after transfection was significantly higher in miRNA-30a- 5p inhibitor group compared to other groups. The results of proliferation markers evaluation also showed decrease of GFRA1, PLZF and ID4 protein in SSCs transfected with miRNA-30a-5p inhibitor compared to the other groups.

Conclusions
It can be concluded that inhibition of miRNA-30a-5p by overexpression of differentiation markers promotes differentiation of Spermatogonial Stem Cells.
HSF1 promotes endometriosis development and glycolysis by up-regulating PFKFB3 expression
Authors: Wang Yixin , Xiu Jing , Yang Tingting , Ren Chune , Yu Zhenhai 
Published: June 2021

Abstract
Background
Endometriosis is a chronic hormonal inflammatory disease characterized by the presence of endometrial tissue outside the uterus. Endometriosis often causes infertility, which brings physical and mental pain to patients and their families.

Methods
We examined the functions of heat shock factor 1 (HSF1) in endometriosis development through cell count assay, cell-scratch assay and clone formation experiments. We used quantitative real-time PCR (qRT-PCR) and Western blot (WB) to detect HSF1 expression. Glucose and lactate levels were determined using a glucose (GO) assay kit and a lactate assay kit. Furthermore, we used a HSF1 inhibitor-KRIBB11 to establish a mouse model of endometriosis.

Results
Our data demonstrated that HSF1 promoted endometriosis development. Interestingly, HSF1 enhanced glycolysis via up-regulating PFKFB3 expression in endometriosis cells, which was a key glycolysis enzyme. Consistently, the HSF1 inhibitor KRIBB11 could abrogate endometriosis progression in vivo and in vitro.

Conclusions
Findings indicate that HSF1 plays an important role in endometriosis development, which might become a new target for the treatment of endometriosis.

Electronic supplementary material
Supplementary data are available.
Increased risk of pulmonary and extrapulmonary tuberculosis infection in patients with polycystic kidney disease: a nationwide population-based study with propensity score-matching analysis
Authors: Chiu Ting-Fang , Yu Tung-Min , Chiu Chih-Wei , Lee Brian K. , Lan Tsuo-Hung , Li Chi-Yuan , Lin Mei-Chen , Kao Chia-Hung 
Published: June 2021

Abstract
Background
Polycystic kidney disease (PKD) is a common renal disorder affecting approximately 1 in 1000 live births. Tuberculosis (TB) is an infectious disease worldwide. This study investigated the risk of TB infection in patients with PKD.

Methods
A nationwide population-based cohort study was performed using Taiwan’s National Health Insurance Research Database. We used patients’ hospitalization files for the entire analysis during 2000–2012. As per diagnosis, we divided patients into PKD and non-PKD cohorts and the major outcome was TB infection.

Results
A total of 13,540 participants with 6770 patients in each cohort were enrolled. The PKD cohort had a higher risk of TB infection than did the non-PKD cohort after adjusting for age, sex, and comorbidities (adjusted hazard ratio (aHR) = 1.91, 95% confidence interval [CI] = 1.51–2.43). When classifying by sites of pulmonary TB (PTB) and extrapulmonary TB (EPTB), the PKD cohort demonstrated a significantly higher risk of EPTB (aHR = 2.44, 95% CI = 1.46–4.08) as well as a risk of PTB (aHR = 1.69, 95% CI = 1.29–2.22). When stratified by the presence or absence of a comorbidity, high TB infection risk was noted in the PKD patients without any comorbidity (HR = 2.69, 95% CI = 1.69–4.30).

Conclusions
Taken together, our findings suggest that PKD is associated with a 1.91-fold increased risk of TB infection. Medical professionls should maintain a high index of suspicion in daily practice for patients with PKD, particularly those with EPTB infection.
Simple rapid in vitro screening method for SARS-CoV-2 anti-virals that identifies potential cytomorbidity-associated false positives
Authors: Yan Kexin , Rawle Daniel J. , Le Thuy T. , Suhrbier Andreas 
Published: June 2021

Abstract
Background
The international SARS-CoV-2 pandemic has resulted in an urgent need to identify new anti-viral drugs for treatment of COVID-19. The initial step to identifying potential candidates usually involves in vitro screening that includes standard cytotoxicity controls. Under-appreciated is that viable, but stressed or otherwise compromised cells, can also have a reduced capacity to replicate virus. A refinement proposed herein for in vitro drug screening thus includes a simple growth assay to identify drug concentrations that cause cellular stress or “cytomorbidity”, as distinct from cytotoxicity or loss of viability.

Methods
A simple rapid bioassay is presented for antiviral drug screening using Vero E6 cells and inhibition of SARS-CoV-2 induced cytopathic effects (CPE) measured using crystal violet staining. We use high cell density for cytotoxicity assays, and low cell density for cytomorbidity assays.

Results
The assay clearly illustrated the anti-viral activity of remdesivir, a drug known to inhibit SARS-CoV-2 replication. In contrast, nitazoxanide, oleuropein, cyclosporine A and ribavirin all showed no ability to inhibit SARS-CoV-2 CPE. Hydroxychloroquine, cyclohexamide, didemnin B, γ-mangostin and linoleic acid were all able to inhibit viral CPE at concentrations that did not induce cytotoxicity. However, these drugs inhibited CPE at concentrations that induced cytomorbidity, indicating non-specific anti-viral activity.

Conclusions
We describe the methodology for a simple in vitro drug screening assay that identifies potential anti-viral drugs via their ability to inhibit SARS-CoV-2-induced CPE. The additional growth assay illustrated how several drugs display anti-viral activity at concentrations that induce cytomorbidity. For instance, hydroxychloroquine showed anti-viral activity at concentrations that slow cell growth, arguing that its purported in vitro anti-viral activity arises from non-specific impairment of cellular activities. The cytomorbidity assay can therefore rapidly exclude potential false positives.
Panoramic prediction equations to estimate implant- to-mandibular canal dimensions in the mandibular posterior region: implications for dental implant treatment
Authors: Bertram Annika , Eckert Alexander W. , Kolk Andreas , Emshoff Rüdiger 
Published: June 2021

AbstractBackgroundTo develop and cross-validate site-specific panoramic radiography (PAN) analysis prediction equations of implant-to-mandibular canal dimensions (IMCD) in mandibular regions posterior to the mental foramen, and to help determine in which instances CBCT technology will be a justified adjunct in clinical practice.MethodsIMCD by PAN (Pan-D) from implant site-specific regions (first premolar, second premolar, first molar, and second molar sites) were collected from 40- to 70-year-old adolescents. They were randomly assigned to validation (n = 144) and cross-validation (n = 148) groups. The cone-beam computed tomography (CBCT) technique was used as the criterion method for the estimation of IMCD (CBCT-D). The PAN analysis equations were developed using stepwise multiple regression analysis and cross-validated using the Bland–Altman approach.ResultsThere was a significant relationship between PAN-D and CBCT-D for both validation (R2 = 57.8 %;p < .001) and cross-validation groups (R2 = 52.5 %;p < .001). Root means-squared error (RMSE) and pure error (PE) were highest for the first molar (RMSE = 1.116 mm, PE = 1.01 mm) and the second molar region (RMSE = 1.162 mm, PE = 1.11 mm).ConclusionsPAN-D has the potential to be developed as an indirect measure of IMCD. However, the findings suggest to exclude scoring of the first and second molars when assessing IMCD via PAN. Use of CBCT may be justified for all IMCD estimations in the first and second molars regions.Trial registrationThis study has been registered and approved by the Ethics Committee of the Martin-Luther University, Halle, Germany (2020-034).
Abstaining from symptomatic implants of modified tension band wiring by nonabsorbable suture fixation for transverse patella fractures
Authors: Jirangkul Puripun , Kosiyatrakul Arkaphat 
Published: June 2021

Abstract
Background
Modified tension band fixation has become commonly used for transverse patella fractures. The conventional stainless steel wire provides sufficient stability but may be associated with complications.

Objective
The study aimed to evaluate the effectiveness of a new modified tension band fixation technique for transverse patella fractures using a nonabsorbable suture.

Material and methods
We present the result of a prospective series using a nonabsorbable suture (FiberWire) for transverse patella fractures. The mean follow-up period totaled 12 months. A total of 16 patients were evaluated by radiographic and clinical review. The postoperative clinical evaluation employed Lysholm and Böstman scores.

Result
All clinical results on follow-up were good to excellent. Minimal intra-articular joint stepping and further fracture displacement were recorded. No patient needed re-operation, and functional outcomes of the knee were satisfactory. No significant differences were found between the injured and contralateral knee range of motion. No symptomatic implants and skin complications were noted, and all fractures were completed heal within 15 weeks.

Conclusion
FiberWire provided sufficient stability and reduced postoperative complications. The results proved appropriate, and the technique has merit, as it obviates the need for re-operation.