bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mechanistic study of the cause of decreased blood 1,25-Dihydroxyvitamin D in sepsis
Authors: Li Chih-Huang , Tang Xiaolei , Wasnik Samiksha , Wang Xiaohua , Zhang Jintao , Xu Yi , Lau Kin-Hing William , Nguyen H. Bryant , Baylink David J. 
Published: December 2019

AbstractBackgroundVitamin D deficiency, determined by blood levels of 25-hydroxyvitamin D [25(OH) D, i.e. the major vitamin D form in blood], has been shown to associate with all-cause mortalities. We recently demonstrated that blood levels of 1,25-dihydroxyvitamin D [1,25(OH)2D, i.e. the active vitamin D] were significantly lower in non-survivors compared to survivors among sepsis patients. Unexpectedly, despite the well documented roles of 1,25(OH)2D in multiple biological functions such as regulation of immune responses, stimulation of antimicrobials, and maintenance of barrier function, 1,25(OH)2D supplementation failed to improve disease outcomes. These previous findings suggest that, in addition to 1,25(OH)2D deficiency, disorders leading to the 1,25(OH)2D deficiency also contribute to mortality among sepsis patients. Therefore, this study investigated the mechanisms leading to sepsis-associated 1,25(OH)2D deficiency.MethodsWe studied mechanisms known to regulate kidney 25-hydroxylvitamin D 1α-hydroxylase which physiologically catalyzes the conversion of 25(OH) D into 1,25(OH)2D. Such mechanisms included parathyroid hormone (PTH), insulin-like growth factor 1 (IGF-1), fibroblast growth factor 23 (FGF-23), and kidney function.ResultsWe demonstrated in both human subjects and mice that sepsis-associated 1,25(OH)2D deficiency could not be overcome by increased production of PTH which stimulates 1α-hydroxylase. Further studies showed that this failure of PTH to maintain blood 1,25(OH)2D levels was associated with decreased blood levels of IGF-1, increased blood levels of FGF-23, and kidney failure. Since the increase in blood levels of FGF-23 is known to associate with kidney failure, we further investigated the mechanisms leading to sepsis-induced decrease in blood levels of IGF-1. Our data showed that blood levels of growth hormone, which stimulates IGF-1 production in liver, were increased but could not overcome the IGF-1 deficiency. Additionally, we found that the inability of growth hormone to restore the IGF-1 deficiency was associated with suppressed expression and signaling of growth hormone receptor in liver.ConclusionsBecause FGF-23 and IGF-1 have multiple biological functions besides their role in regulating kidney 1α-hydroxylase, our data suggest that FGF-23 and IGF-1 are warranted for further investigation as potential agents for the correction of 1,25(OH)2D deficiency and for the improvement of survival among sepsis patients.
Nasopharyngeal carriage, spa types and antibiotic susceptibility profiles of Staphylococcus aureus from healthy children less than 5 years in Eastern Uganda
Authors: Kateete David Patrick , Asiimwe Benon B. , Mayanja Raymond , Mujuni Brian , Bwanga Freddie , Najjuka Christine F. , Källander Karin , Rutebemberwa Elizeus 
Published: December 2019

Abstract
Background
Staphylococcus aureus carriage is a known risk factor for staphylococcal disease. However, the carriage rates vary by country, demographic group and profession. This study aimed to determine the S. aureus carriage rate in children in Eastern Uganda, and identify S. aureus lineages that cause infection in Uganda.

Methods
Nasopharyngeal samples from 742 healthy children less than 5 years residing in the Iganga/Mayuge Health and Demographic Surveillance Site in Eastern Uganda were processed for isolation of S. aureus. Antibiotic susceptibility testing based on minimum inhibitory concentrations (MICs) was determined by the BD Phoenix™ system. Genotyping was performed by spa and SCCmec typing.

Results
The processed samples yielded 144 S. aureus isolates (one per child) therefore, the S. aureus carriage rate in children was 19.4% (144/742). Thirty one percent (45/144) of the isolates were methicillin resistant (MRSA) yielding a carriage rate of 6.1% (45/742). All isolates were susceptible to rifampicin, vancomycin and linezolid. Moreover, all MRSA were susceptible to vancomycin, linezolid and clindamycin. Compared to methicillin susceptible S. aureus (MSSA) isolates (68.8%, 99/144), MRSA isolates were more resistant to non-beta-lactam antimicrobials –trimethoprim/sulfamethoxazole 73.3% (33/45) vs. 27.3% (27/99) [p < 0.0001]; erythromycin 75.6% (34/45) vs. 24.2% (24/99) [p < 0.0001]; chloramphenicol 60% (27/45) vs. 19.2% (19/99) [p < 0.0001]; gentamicin 55.6% (25/45) vs. 25.3% (25/99) [p = 0.0004]; and ciprofloxacin 35.6% (16/45) vs. 2% (2/99) [p < 0.0001]. Furthermore, 42 MRSA (93.3%) were multidrug resistant (MDR) and one exhibited high-level resistance to mupirocin. Overall, 61 MSSA (61.6%) were MDR, including three mupirocin and clindamycin resistant isolates. Seven spa types were detected among MRSA, of which t037 and t064 were predominant and associated with SCCmec types I and IV, respectively. Fourteen spa types were detected in MSSA which consisted mainly of t645 and t4353.

Conclusions
S. aureus carriage rate in healthy children in Eastern Uganda is high and comparable to rates for hospitalized patients in Kampala. The detection of mupirocin resistance is worrying as it could rapidly increase if mupirocin is administered in a low-income setting. S. aureus strains of spa types t064, t037 (MRSA) and t645, t4353 (MSSA) are prevalent and could be responsible for majority of staphylococcal infections in Uganda.
Efficacy and safety of sodium zirconium cyclosilicate in patients with baseline serum potassium level ≥ 5.5 mmol/L: pooled analysis from two phase 3 trials
Authors: Amin Alpesh N. , Menoyo Jose , Singh Bhupinder , Kim Christopher S. 
Published: December 2019

Abstract
Background
Reliable, timely-onset, oral treatments with an acceptable safety profile for patients with hyperkalemia are needed. We examined the efficacy and safety of sodium zirconium cyclosilicate (SZC; formerly ZS-9) treatment for ≤ 48 h in patients with baseline serum potassium level ≥ 5.5 mmol/L.

Methods
Data were pooled from two phase 3 studies (ZS-003 and HARMONIZE) among patients receiving SZC 10 g three times daily. Outcomes included mean and absolute change from baseline, median time to potassium level ≤ 5.5 and ≤ 5.0 mmol/L, and proportion achieving potassium level ≤ 5.5 and ≤ 5.0 mmol/L at 4, 24, and 48 h. Outcomes were stratified by baseline potassium. Safety outcomes were evaluated.

Results
At baseline, 125 of 170 patients (73.5%) had potassium level 5.5–< 6.0, 39 (22.9%) had potassium level 6.0–6.5, and 6 (3.5%) had potassium level > 6.5 mmol/L. Regardless of baseline potassium, mean potassium decreased at 1 h post-initial dose. By 4 and 48 h, 37.5% and 85.0% of patients achieved potassium level ≤ 5.0 mmol/L, respectively. Median (95% confidence interval) times to potassium level ≤ 5.5 and ≤ 5.0 mmol/L were 2.0 (1.1–2.0) and 21.6 (4.1–22.4) h, respectively. Fifteen patients (8.8%) experienced adverse events; none were serious.

Conclusions
SZC 10 g three times daily achieved serum potassium reduction and normokalemia, with a favorable safety profile.

Trial registration
ClinicalTrials.gov identifiers: ZS-003: NCT01737697 and HARMONIZE: NCT02088073.
Management of anticoagulation and antiplatelet therapy in patients with primary membranous nephropathy
Authors: Zou Honghong , Li Yebei , Xu Gaosi 
Published: December 2019

Abstract
Background
It has been recognized that primary membranous nephropathy (MN) is related to an increased risk for thromboembolic complications. However, the current evidence supporting prophylactic and therapeutic anticoagulation is too weak to better meet the clinical needs of this patient population. The present review provides some suggestions to guide the decision on anticoagulant management in primary MN patients with a high risk of thrombosis or with thromboembolic complication.

Materials and methods
We extracted relevant studies by searching the published literature using the Cochrane Library, Medline, PubMed and Web of Science from March 1968 to March 2018. Eligible publications included guidelines, reviews, case reports, and clinical trial studies that concerned the rational management of anticoagulation therapy in the primary MN population. The evidence was thematically synthesized to contextualize implementation issues.

Results
It was helpful for clinicians to make a decision for personalized prophylactic aspirin or warfarin in primary MN patients when serum albumin was < 3.2 g/dl to prevent arterial and venous thromboembolic events (VTEs). The treatment regimen for thromboembolic complications (VTEs, acute coronary syndrome and ischemic stroke) in primary MN was almost similar to that for the general population with thromboembolic events. It is noteworthy that patients should continue the previous primary MN treatment protocol during the entire treatment period until they achieve remission, the protocol is complete and the underlying diseases resolve.

Conclusion
The utility of prophylactic aspirin or warfarin may have clinical benefits for the primary prevention of thromboembolic events in primary MN with hypoalbuminemia. It is necessary to perform large randomized controlled trials and to formulate relevant guidelines to support the present review.
Relationship between renal tissues phospholipase A2 receptor and its serum antibody and clinical condition and prognosis of idiopathic membranous nephropathy: a meta-analysis
Authors: Dong Dan , Fan Ting-ting , Wang Ying-ying , Zhang Lu , Song Li , Zhang Li 
Published: December 2019

Abstract
Objective
To investigate the correlation of M-type phospholipase A2 receptor (PLA2R) expression and serum anti-PLA2R antibody with the clinical parameters and prognosis of patients with idiopathic membranous nephropathy (IMN).

Methods
A literature search for relevant original articles published between January 2009 and October 2019 was conducted on domestic and foreign databases. RevMan 5.3 software was used for meta-analysis.

Results
Eighteen studies were included in this meta-analysis. There were 1235 anti-PLA2R antibody-positive and PLA2R-positive patients, and 407 serum anti-PLA2R antibody-negative and PLA2R-negative patients. Compared with negative group, patients in the serum PLA2R antibody -positive group had lower serum albumin [SMD = -1.11, 95% CI (− 1.82, − 0.40), P < 0.00001], higher age [MD = 2.71, 95% CI (1.94, 3.48), P < 0.00001], and lower estimated glomerular filtration rate (eGFR) [MD = -10.34, 95% CI (− 12.09, − 8.60), P < 0.00001]; no significant between-group difference was observed with respect to 24-h urine protein and serum creatinine. However, no significant difference was observed between renal tissues PLA2R -positive and -negative groups with respect to serum albumin, eGFR, serum creatinine, and 24-h urine protein. Remission rate in the serum anti-PLA2R antibody -positive group was lower than that in the -negative group [OR = 0.41, 95% CI (0.28, 0.61),P < 0.00001]; however, no significant between-group difference in this respect was observed between the renal tissue PLA2R-positive and -negative groups. In the serum anti-PLA2R antibody -positive group, the higher titer subgroup had lower remission rate [OR = 0.19, 95% CI (0.07, 0.55),P = 0.002]. No significant difference was observed between anti-PLA2R antibody -positive and -negative groups with respect to adverse events. Serum anti-PLA2R antibody titer did not affect the adverse event rate.

Conclusion
As compared to PLA2R, serum anti-PLA2R antibody is more closely related with IMN disease progression.
PPARα ligand, AVE8134, and cyclooxygenase inhibitor therapy synergistically suppress lung cancer growth and metastasis
Authors: Wu Lujin , Wang Wei , Dai Meiyan , Li Huihui , Chen Chen , Wang Daowen 
Published: December 2019

AbstractBackgroundLung cancer (LC) is one of the leading causes of death worldwide, which highlights the urgent need for better therapies. Peroxisome proliferator-activated nuclear receptor alpha (PPARα), known as a key nuclear transcription factor involved in glucose and lipid metabolism, has been also implicated in endothelial proliferation and angiogenesis. However, the effects and potential mechanisms of the novel PPARα ligand, AVE8134, on LC growth and progression remain unclear.MethodsA subcutaneous tumour was established in mice by injecting TC-1 lung tumour cells (~ 1 × 106cells) into their shaved left flank. These mice were treated with three different PPARα ligands: AVE8134 (0.025% in drinking water), Wyeth-14,643 (0.025%), or Bezafibrate (0.3%). Tumour sizes and metastasis between treated and untreated mice were then compared by morphology and histology, and the metabolites of arachidonic acid (AA) were detected by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Inhibition of either Cyp2c44 expression by genetic disruption or cyclooxygenase (COX) activity by indomethacin was used to test the mechanisms by which AVE8134 affects tumour growth.ResultsThe pharmacodynamics effects of AVE8134, Wyeth-14,643, and Bezafibrate on lipids control were similar. However, their effects on tumour suppression were different. Eicosanoid profile analysis showed that all PPARα ligands reduced the production of AA-derived epoxyeicosatrienoic acids (EETs) and increased the hydroxyl product, 11-hydroxyeicosatetraenoic acids (11-HETE). Moreover, increased 11-HETE promoted endothelial proliferation, angiogenesis, and subsequent tumour deterioration in a dose-dependent manner possibly via activating the AKT/extracellular signal-regulated kinase (ERK) pathway. The increased 11-HETE partly neutralized the benefits provided by the Cyp2c44-EETs system inhibited by PPARα ligands in tumour-bearing mice. AVE8134 treatment worsened the tumour phenotype in Cyp2c44 knockout mice, indicating that AVE8134 has contradictory effects on tumour growth. The COX inhibitor indomethacin strengthened the inhibitory actions of AVE8134 on tumour growth and metastasis by inhibiting the 11-HETE production in vivo and in vitro.ConclusionIn this study, we found that the degrees of inhibition on LC growth and metastasis by PPARα ligands depended on their bidirectional regulation on EETs and 11-HETE. Considering their safety and efficacy, the novel PPARα ligand, AVE8134, is a potentially ideal anti-angiogenesis drug for cancer treatment when jointly applied with the COX inhibitor indomethacin.
Intraocular pressure-lowering effects of Ripasudil: a potential outcome marker for Trabeculotomy
Authors: Goda Erina , Hirooka Kazuyuki , Mori Kazuhiko , Kiuchi Yoshiaki 
Published: December 2019

AbstractBackgroundTo examine the use of ripasudil as a trabeculotomy outcome marker in patients with primary open-angle glaucoma (POAG).MethodsBetween May 2015 and December 2018, 35 eyes underwent trabeculotomy and were postoperatively followed for over 3 months. Ripasudil was defined as effective if drug administration resulted in a greater than 10% reduction in intraocular pressure (IOP). Patients were divided into effective (effective group) or non-effective (non-effective group) ripasudil administration groups. The need for additional glaucoma surgery or an IOP ≥ 21 mmHg indicated surgical failure. In both groups, a Kaplan-Meier survival-analysis was used to evaluate success probabilities related to postoperative IOP levels.ResultsEffective IOP reduction occurred in 14 of 35 eyes after ripasudil administration, which was shown by a decrease of more than 10%. Postoperatively, both groups exhibited significant reductions of IOP and antiglaucoma medication use for up to 24 months. At 12 and 24 months after trabeculotomy, probabilities of success in the effective vs. non-effective group were 100% vs. 94.7 and 100% vs. 75.4%, respectively (P = 0.14).ConclusionsTrabeculotomy is effective for achieving an IOP < 21 mmHg in ripasudil effective POAG eyes. Examination of ripasudil’s IOP-lowering effects may be useful in predicting surgical outcomes after trabeculotomy.
Rapid cycling bipolar disorder is associated with antithyroid antibodies, instead of thyroid dysfunction
Authors: Gan Zhaoyu , Wu Xiuhua , Chen Zhongcheng , Liao Yingtao , Wu Yingdong , He Zimeng , Yang Zhihua , Zhang Qi 
Published: December 2019

Abstract
Background
Conclusions regarding the association between antithyroid antibodies or thyroid dysfunction and rapid cycling bipolar disorder (RCBD) have been conflicting. Previous studies suggest that the impact of antithyroid antibodies on mental wellbeing seems to be independent of thyroid function. Here, we investigated their independent association with RCBD in a large, well-defined population of bipolar disorder (BD).

Methods
Fast serum levels of free thyroxine (FT4), free triiodothyronine (FT3), thyroid Stimulating Hormone (TSH), TPO-abs and Tg-abs were simultaneously measured in 352 patients with BD. Clinical features of BD were collected through semi-structural interview conducted by trained interviewers with background of psychiatric education.

Results
Neither hypothyroidism nor hyperthyroidism was significantly associated with RCBD. Both TPO-abs and Tg-abs were significantly related to RCBD, even after controlling for gender, age, marriage status, education, antidepressants treatment, comorbidity of thyroid diseases, and thyroid function (serum levels of FT3, FT4 and TSH). Although TPO-abs and Tg-abs were highly correlated with each other, binary logistic regression with forward LR selected TPO-abs, instead of Tg-abs, to be associated with RCBD. TPO-abs was significantly, independently of Tg-abs, associated with hyperthyroidism, while Tg-abs was marginally significantly related to hypothyroidism at the presence of TPO-abs.

Conclusion
TPO-abs might be treated as a biomarker of RCBD. Further exploring the underlying mechanism might help understand the nature of RCBD and find out new treatment target for it.
Quality of care for children with severe disease in the Democratic Republic of the Congo
Authors: Clarke-Deelder Emma , Shapira Gil , Samaha Hadia , Fritsche György Bèla , Fink Günther 
Published: December 2019

Abstract
Background
Despite the almost universal adoption of Integrated Management of Childhood Illness (IMCI) guidelines for the diagnosis and treatment of sick children under the age of five in low- and middle-income countries, child mortality remains high in many settings. One possible explanation of the continued high mortality burden is lack of compliance with diagnostic and treatment protocols. We test this hypothesis in a sample of children with severe illness in the Democratic Republic of the Congo (DRC).

Methods
One thousand one hundred eighty under-five clinical visits were observed across a regionally representative sample of 321 facilities in the DRC. Based on a detailed list of disease symptoms observed, patients with severe febrile disease (including malaria), severe pneumonia, and severe dehydration were identified. For all three disease categories, treatments were then compared to recommended case management following IMCI guidelines.

Results
Out of 1180 under-five consultations observed, 332 patients (28%) had signs of severe febrile disease, 189 patients (16%) had signs of severe pneumonia, and 19 patients (2%) had signs of severe dehydration. Overall, providers gave the IMCI-recommended treatment in 42% of cases of these three severe diseases. Less than 15% of children with severe disease were recommended to receive in-patient care either in the facility they visited or in a higher-level facility.

Conclusions
These results suggest that adherence to IMCI protocols for severe disease remains remarkably low in the DRC. There is a critical need to identify and implement effective approaches for improving the quality of care for severely ill children in settings with high child mortality.
Increasing the proportion of healthier foods available with and without reducing portion sizes and energy purchased in worksite cafeterias: protocol for a stepped-wedge randomised controlled trial
Authors: Reynolds James P. , Kosīte Daina , Rigby Dames Brier , Brocklebank Laura A. , Pilling Mark , Pechey Rachel , Hollands Gareth J. , Marteau Theresa M. 
Published: December 2019

Abstract
Background
Overconsumption of energy from food contributes to high rates of overweight and obesity in many populations. A promising set of interventions tested in pilot studies in worksite cafeterias, suggests energy intake may be reduced by increasing the proportion of healthier – i.e. lower energy – food options available, and decreasing portion sizes. The current study aims to assess the impact on energy purchased of i. increasing the proportion of lower energy options available; ii. combining this with reducing portion sizes, in a full trial.

Methods
A stepped-wedge randomised controlled trial in 19 worksite cafeterias, where the proportion of lower energy options available in targeted food categories (including main meals, snacks, and cold drinks) will be increased; and combined with reduced portion sizes. The primary outcome is total energy (kcal) purchased from targeted food categories using a pooled estimate across all sites. Follow-up analyses will test whether the impact on energy purchased varies according to the extent of intervention implementation.

Discussion
This study will provide the most reliable estimate to date of the effect sizes of two promising interventions for reducing energy purchased in worksite cafeterias.

Trial registration
The study was prospectively registered on ISRCTN (date: 24.05.19; TRN: ISRCTN87225572; doi: 10.1186/ISRCTN87225572).
A model to explain self-medication by Iranian people: a qualitative grounded theory study
Authors: Fereidouni Zhila , Najafi Kalyani Majid 
Published: December 2019

Abstract
Background
Self-medication (SM) is a common and global health problem. The process of attempting SM is still unclear. Exploration of SM and its contributing factors would help policymakers design and develop preventive programs. This qualitative study aimed to explore the process of attempting SM among Iranian people.

Methods
This grounded theory (GT) study was conducted among people with the experience of attempting SM (n = 17) and medical staff (n = 9) in Iran selected via semi-structured interviews. The recorded and transcribed interviews were analyzed using open, axial, and selective coding based on Strauss and Corbin’s (1998) approach.

Results
The study results revealed that people sought to deal as simply and quickly as possible with their illnesses/symptoms according to their attitudes towards and perceptions of illnesses/symptoms as well as their economic and social problems. This simple and quick approach was the participants’ main concern, resulting in taking decision-making strategies as SM facilitators. SM, in turn, provided short-term improvement and temporary satisfaction as a predominant outcome. Overall, “to avoid being trapped in the vortex of illness” was the central category, which covered and connected all the other categories developed in this study.

Conclusions
The elements of this model could be used as a guide for healthcare policymakers to design preventive programs and to plan for increasing people’s knowledge about the complications and consequences of SM. In addition, identification of barriers to referral to physicians and treatment of illnesses through the right way as well as reducing the health system’s problems would help reduce SM.