bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cefaclor as a first-line treatment for acute uncomplicated cystitis: a retrospective single-center study
Authors: Koguchi Dai , Murakami Yasukiyo , Ikeda Masaomi , Dobashi Masato , Ishii Junichiro 
Published: March 2020

Abstract
Background: Wide-spectrum antibiotics have been favored to treat acute uncomplicated cystitis (AUC) for a long time, leading to the emergence of multi-drug resistant bacteria. We hypothesize that narrow-spectrum antibiotics might mitigate the issue and aim to investigate the clinical efficacy of cefaclor in patients with AUC.
Methods : We retrospectively reviewed the clinical data of female outpatients with AUC treated with cefaclor and evaluated the safety and clinical efficacy. Clinical cure was defined as the elimination of clinical symptom under 4 white blood cells (WBCs) per high power field on microscopy.
Results : Overall, 223 women with AUC were enrolled. Escherichia coli was the dominant pathogen (n=160; 68.6%), followed by Klebsiella species and E. coli -extended spectrum β-lactamase (ESBL) (n=19; 8.1% and n=18; 7.7%). Overall success rate was 94.0% (n=219) and susceptibility rate of cefazolin was 84.1%, which was close to that of levofloxacin (82.9%). Ampicillin showed the lowest rate of 63.7% with a significantly greater resistance rate of 35.3% among all antibiotics (P<0.001). In the subgroup analysis, the success rate in patients with resistance to levofloxacin or cefazolin was 100% (n=24) or 93.3% (n=14). The rate in patients with resistance to both antibiotics was 60.0% (n=9), and the pathogens in the other 40.0% (n=6) of patients with treatment failure were E. coli -ESBL.
Conclusion : Cefaclor showed excellent efficacy in AUC patients, even in those with in vitro resistance to cefazolin or levofloxacin. Cefaclor may be considered as a first-line option in patients with AUC and a second-line option for those with levofloxacin treatment failure.
The effects of Enhanced Primary Healthcare interventions on primary care providers’ job satisfaction
Authors: Wong Wen Jun , Norzi Aisyah Mohd , Ang Swee Hung , Chan Chee Lee , Jaafar Faeiz Syezri Adzmin , Sivasampu Sheamini 
Published: March 2020

Abstract
Background:
In response to the rising burden of cardiovascular risk factors, the Malaysian government has implemented Enhanced Primary Healthcare (EnPHC) interventions in July 2017 at public clinic level to improve management and clinical outcomes of type 2 diabetes and hypertensive patients. Healthcare providers (HCPs) play crucial roles in healthcare service delivery and health system reform can influence HCPs’ job satisfaction. However, studies evaluating HCPs’ job satisfaction following primary care transformation remain scarce in low- and middle-income countries. This study aims to evaluate the effects of EnPHC interventions on HCPs’ job satisfaction.

Methods:
This is a quasi-experimental study conducted in 20 intervention and 20 matched control clinics. We surveyed all HCPs who were directly involved in patient management. A self-administered questionnaire which included six questions on job satisfaction were assessed on a scale of 1-4 at baseline (April and May 2017) and post-intervention phase (March and April 2019). Unadjusted intervention effect was calculated based on absolute differences in mean scores between intervention and control groups after implementation. Difference-in-differences analysis was used in the multivariable linear regression model and adjusted for providers and clinics characteristics to detect changes in job satisfaction following EnPHC interventions. A negative estimate indicates relative decrease in job satisfaction in the intervention group compared with control group.

Results:
A total of 1042 and 1215 HCPs responded at baseline and post-intervention respectively. At post-intervention, the intervention group reported higher level of stress with adjusted differences of -0.139 (95% CI -0.266,-0.012; p=0.032). Nurses, being the largest workforce in public clinics were the only group experiencing dissatisfaction at post-intervention. In subgroup analysis, nurses from intervention group experienced increase in work stress following EnPHC interventions with adjusted differences of -0.223 (95% CI -0.419,-0.026; p=0.026). Additionally, the same group were less likely to perceive their profession as well-respected at post-intervention (β= -0.175; 95% CI -0.331,-0.019; p=0.027]).

Conclusions:
Our findings suggest that EnPHC interventions had resulted in some untoward effect on HCPs’ job satisfaction. Job dissatisfaction can have detrimental effects on the organisation and healthcare system. Therefore, provider experience and well-being should be considered before introducing healthcare delivery reforms to avoid overburdening of HCPs.
Immunogenicity analysis of conserved fragments in Plasmodium ovale species merozoite surface protein 4
Authors: Uwase Juliette , Chu Ruilin , Kassegne Kokouvi , Lei Yao , Shen Feihu , Fu Haitian , Sun Yifan , Xuan Yinghua , Cao Jun , Cheng Yang 
Published: March 2020

Abstract
Background : There is an urgent need for an effective vaccine to control and eradicate malaria, one of the most serious global infectious diseases. Plasmodium merozoite surface protein 4 (MSP4) has been listed as a blood-stage subunit vaccine candidate for malaria. Plasmodium ovale species (spp.) infection is also a source of malaria burden in tropical regions where it is sometimes mixed with other Plasmodium species. However, little is known about P. ovale spp. MSP4. Methods : The msp4 gene was amplified through polymerase chain reaction using genomic DNA extracted from blood samples of 46 patients infected with P. ovale spp. and amplified products were sequenced. Open reading frames predicted as immunogenic peptides consisting of 119 and 97 amino acids of P. ovale curtisi MSP4 (PocMSP4) and P. ovale wallikeri MSP4 (PowMSP4), respectively, were selected for protein expression. Recombinant proteins (rPoMSP4) were expressed in Escherichia coli , purified, analyzed, and immunized in BALB/c mice. The specificity of anti-MSP4-immunoglubulin (Ig) G antibodies was evaluated by Western blot and enzyme-linked immunosorbent assays, and cellular immune responses were analyzed via lymphocyte proliferation assays. Results : Full peptide sequences of PocMSP4 and PowMSP4 were completely conserved in all clinical isolates, except in the epidermal growth factor-like domain at the carboxyl terminus where only one mutation was observed in one P. ovale wallikeri isolate. Furthermore, we successfully expressed the truncated pocmsp4 and powmsp4 and purified as ~32 kDa proteins. Our results showed that PocMSP4 and PowMSP4 induced high antibody responses with end-point titers ranging from 1:10,000 to 1:2,560,000 in all immunized mouse groups and with high IgG avidity to PocMSP4 (80.5%) and PowMSP4 (92.3%). Furthermore, rPocMSP4 and rPowMSP4 cross-reacted with anti-PowMSP4-specific or anti-PocMSP4-specific antibodies. Additionally, anti-PoMSP4 IgG antibodies showed broad immuno-specificity in reacting against rPoMSP1 and rPoAMA1. Lastly, PocMSP4- and PowMSP4-immunized mice induced cellular immune responses with PocMSP4 (36%) and PowMSP4 cells (15.8%) as observed through splenocyte proliferation assays. Conclusion : Our study suggested conservation in PoMSP4 protein sequences and high immunogenicity was observed in rPoMSP4. Furthermore, PocMSP4- and PowMSP4-immunized mice induced cellular immune responses, suggesting that both humoral and cellular immune responses play crucial roles in the protection against any antigen.
Impact of perioperative hemodynamic optimization therapies in surgical patients: Economic study and Meta-analysis
Authors: Silva João M , Menezes Pedro Ferro L , Lobo Suzana M , Carvalho Flavia Helena S , Oliveira Mariana Augusta N , Filho Francisco Nilson F Cardoso , Fernando Bruna N , Carmona Maria Jose C , Teich Vanessa D , Malbouisson Luiz Marcelo S 
Published: March 2020

Abstract
Background: Several studies suggest that hemodynamic optimization therapies can reduce complications, the length of hospital stay and costs. However, Brazilian data are scarce. Therefore, the objective of this analysis was to evaluate whether the improvement demonstrated by hemodynamic optimization therapy in surgical patients could result in lower costs from the perspective of the Brazilian public unified health system.
Methods: A meta-analysis was performed comparing surgical patients who underwent hemodynamic optimization therapy (intervention) with patients who underwent standard therapy (control) in terms of complications and hospital costs. The cost-effectiveness analysis evaluated the clinical and financial benefits of hemodynamic optimization protocols for surgical patients. The analysis considered the clinical outcomes of randomized studies published in the last 20 years that involved surgeries and hemodynamic optimization therapy. Indirect costs (equipment depreciation, estate and management activities) were not included in the analysis.
Results: A total of 21 clinical trials with a total of 4872 surgical patients were selected. Comparison of the intervention and control groups showed lower rates of infectious (RR=0.66; 95% CI=0.58-0.74), renal (RR=0.68; 95% CI=0.54-0.87), and cardiovascular (RR=0.87; 95% CI=0.76-0.99) complications and a nonstatistically significant lower rate of respiratory complications (RR=0.82; 95% CI=0.67-1.02). There was no difference in mortality (RR=1.02; 95% CI=0.80-1.3) between groups. In the analysis of total costs, the intervention group showed a cost reduction of R$396,024.83-BRL ($90,161.38-USD) for every 1000 patients treated compared to the control group. The patients in the intervention group showed greater effectiveness, with 1.0 fewer days in the intensive care unit and hospital. In addition, there were 333 fewer patients with complications, with a consequent reduction of R$1,630,341.47-BRL ($371,173.27-USD) for every 1000 patients treated.
Conclusions: Hemodynamic optimization therapy is cost-effective and would increase the efficiency of and decrease the burden of the Brazilian public health system.
Serological and Molecular Evidence of Brucella Species in the Rapidly Growing Pig Sector in Kenya
Authors: Akoko James Miser , Pelle Roger , Kivali Velma , Schelling Esther , Shirima Gabriel , Machuka Eunice , Mathew Coletha , Fèvre Eric M. , Kyallo Victoria , Falzon Laura C. , Lukambagire AbdulHamid S. , Halliday Jo E.B. , Bonfoh Bassirou , Kazwala Rudovick , Ouma Collins 
Published: March 2020

Abstract
Background: Brucellosis is an emerging yet neglected zoonosis that has been reported in Kenya. Epidemiological data on brucellosis in ruminants is readily accessible; however, reports on brucellosis in pigs remain limited. This study sought to detect Brucella infection in pig serum by both serological and molecular techniques. Serum from 700 pigs randomly collected at a centralized abattoir in Nairobi region, Kenya were screened in parallel, using both Rose Bengal Test (RBT) and competitive Enzyme-Linked Immuno-sorbent Assay (cELISA) for antibodies against Brucella spp. All sera positive by RBT and 16 randomly selected negative samples were further tested using conventional PCR targeting bcsp31 geneand real-time PCR (RT-PCR) assays targeting IS711 and bcsp31 genes. Results: A prevalence of 0.57% (n = 4/700) was estimated using RBT; none of these samples was positive on cELISA. All RBT positive sera were also positive by both PCRs, while two sero-negative samples also tested positive on RT-PCR (n = 6/20). Brucella abortus was detected in four out of the six PCR positive samples through a real-time multiplex PCR. Conclusion: The detection of antibodies against Brucella spp. and DNA in serum from slaughterhouse pigs confirm the presence of Brucella in pigs. Therefore, investigation of the epidemiology and role of pigs in the transmission of brucellosis in Kenya is needed. Further targeted studies would be useful to systematically quantify and identify the spp. of Brucella in pigs.
Experiences and views of different key stakeholders on the feasibility of treating cancer-related fatigue
Authors: Canella Claudia , Mikolasek Michael , Rostock Matthias , Guckenberger Matthias , Jenewein Josef , Linka Esther , Six Claudia , Stoll Sarah , Stupp Roger , Witt Claudia M. 
Published: March 2020

Abstract
Background: Although cancer-related fatigue (CRF) has gained increased attention in the past decade, therapy remains a challenge. Treatment programs are more likely to be effective if the needs and interests of the persons involved are well represented. This can be achieved by stakeholder engagement.
In this paper, different key stakeholders' experiences and views on the feasibility of treating CRF in the context of supportive care in hospital environments are analyzed.
Method: In a qualitative study with the aim of developing an integrative treatment program for CRF, a total of 22 stakeholders (6 medical oncologists, 5 nurses, 9 patients, 1 patient family member, 1 representative of the Swiss Cancer League) were interviewed either in a face-to-face (n=12) or focus group setting (n=2). For data analyses, the method of qualitative content analysis was used.
Results: The stakeholders referred to different contextual factors when talking about the feasibility of treating CRF in the context of supportive care in hospital environments. These included assessment, reporting and information; treatability; attitude; infrastructure, time-management, costs and affordability; and integrative approach.
Conclusions: Key factors of a feasible treatment approach to CRF are a coherent, cost effective integrative treatment program facilitated by an interdisciplinary team of health care providers. Furthermore, the treatment approach should be patient orientated, adopting an individualized approach. The major challenges of making the integrative treatment program feasible for CRF are resources and interprofessional collaboration.
Rare homozygous mutation in TUBB8 associated with oocyte maturation defect-2 in a consanguineous mating family
Authors: Xing Qiong , Wang Ruyi , Chen Beili , Li Lin , Pan Hong , Li Tengyan , Ma Xu , Cao Yunxia , Wang Binbin 
Published: March 2020

Abstract
Purpose: Variations in many genes may lead to the occurrence of oocyte maturation defects. To investigate the genetic basis of oocyte maturation defects, we performed clinical and genetic analysis of a pedigree.
Methods: The proband with oocyte maturation defect-2 receiving ovulation induction therapy and her parents were selected for clinical detection, whole exome sequencing and Sanger sequencing. One unrelated healthy woman received ovulation induction therapy as control. Mutations were assessed after frequency screening of public exome databases. Then homozygous variants shared by the proband and her parents were selected.
Results: Arrest of oocytes maturation was observed. A new missense mutation in TUBB8 (TUBB8: NM_177987: exon 2: c. C161T: p. A54V) was identified, which was shown to be rare compared with public databases. The variant was highly conserved among primates, and was suggested to be deleterious by online software prediction.
Conclusions: The homozygote of this variant (TUBB8: NM_ 177987: exon 2:c.C161T: p.A54V) might affect spindle assembly, cause arrest of oocyte maturation and lead to oocyte maturation defect-2.
The Effect of Posterior Capsule Repair in Total Hip Arthroplasty：A Systematic Review and Meta-Analysis
Authors: Sun Xiaobo , Zhu Xingyang , Zeng Yuqing , Zhang Haitao , Zeng Jianchun , Feng Wenjun , Li Jie , Zeng Yirong 
Published: March 2020

Abstract
Background: Prior studies have compared the posterior capsule repair group in primary total hip arthroplasty by posterior approach with the control group without posterior capsule repair suggesting that the posterior capsule repair group had better clinical outcomes. However, it is still a controversy which treatment is more helpful for hip diseases. The purpose of our article is to obtain the postoperative outcomes between the 2 procedures. Methods: We performed a systematic search by browsing the MEDLINE, EMBASE, Cochrane Library. There is no restriction on the date of publication. Before we submit our manuscript, we have re-searched the literatures again, including the articles which directly compared the postoperative outcomes of the 2 procedures. Results: A total of 8 comparative studies were included in our meta-analysis. The posterior capsule repair group showed less dislocation rate, higher HHS, and even less postoperative bleeding volume. Meanwhile, there is no significant difference in ROM between 2 groups. Conclusion: In conclusion, according to current evidences, repairing posterior capsule during primary THA may have better functional outcomes, less dislocation incidence, and less loss of blood.
Distinct clinical and prognostic implication of IDH1/2 mutation and other most frequent mutations in large duct and small duct subtypes of intrahepatic cholangiocarcinoma
Authors: Ma Bingqi , Meng Huijuan , Tian Ye , Wang Yingying , Song Tianqiang , Zhang Ti , Wu Qiang , Cui Yunlong , Li Huikai , Zhang Wei , Li Qiang 
Published: March 2020

Abstract
Background: Isocitrate dehydrogenase 1/2 (IDH1/2), BAP1, ARID1A and PBRM1 have been reported as the most frequent mutant genes in intrahepatic cholangiocarcinoma (ICC), and their relationships with clinicopathological features and prognosis were researched in this study.
Methods: We collected clinical data of 130 ICC patients from January 2012 to December 2017. The IDH1/2 mutation and loss of BAP1, ARID1A and PBRM1 expressions were detected by DNA sequencing or immunohistochemical methods, and histological subtype of ICCs was determined by hematoxylin-eosin, Alcian blue and S100P staining.
Results: IDH1/2 mutation was related to decreased preoperative serum total bilirubin (P=0.039), ferritin (P=0.000) and higher histological differentiation (P=0.024), and was associated with prolonged disease-free surviva l (P=0.009) and a trend toward increased overall survival (P=0.126) in small duct type of ICCs. Immunohistochemical staining results of MsMab-1 were generally consistent with DNA sequencing for IDH1/2 mutant in ICCs (κ= 0.691). Only BAP1 expression loss was correlated to prolonged disease-free survival (P=0.031) and overall survival (P=0.041) in large duct type of ICCs.
Conclusions : IDH1/2 mutation is a favorable predictor and may be related to iron metabolism in small duct type of ICCs. Furthermore, we suggest that the detection of IDH1/2 mutation is indispensable to determine targeted therapy in small duct type ICCs, while it is not necessary in large duct of ICCs. MsMab-1 is a relatively effective multi-specific antibody against IDH1/2 mutant in ICCs. BAP1 expression loss was correlated with improved prognosis only in large duct type ICCs.
Time-dependent changes in FT4 and FT3 levels measured using mass spectrometry after an acute ingestion of excess levothyroxine in a case with hypothyroidism
Authors: Ito Yuko , Suzuki Satoru , Matsumoto Yoshiko , Ohkouchi Chiyo , Suzuki Satoshi , Iwadate Manabu , Midorikawa Sanae , Yokoya Susumu , Suzuki Shinichi , Shimura Hiroki 
Published: March 2020

Abstract
Background: Thyrotoxicosis is common disorder among endocrine dysfunctions. It is not rare that the free thyroid hormone level exceeds the measurement range of immunoassay. Such extreme high concentration of free thyroid hormone is generally considered to be impossible to measure correctly because of changes in the balance between free hormones and binding proteins by dilution of serum. Using liquid chromatography-tandem mass spectrometry (LC-MS/MS), however, higher concentrations are able to be determined.
Case presentation: We present a case of a 21-year-old female with congenital hypothyroidism who had taken a total of 5 mg levothyroxine over three consecutive days following discontinuance of the medication for a month. Immunoassay performed three hours after the last ingestion showed that the patient’s free thyroxine (FT4) was over 100 pmol/L and her free triiodothyronine (FT3) was 24.5 pmol/L. With a temporary cessation of levothyroxine, the patient was kept for observation without any other medication. Two days after the last ingestion, FT4 was still over 100 pmol/L and FT3 was increased to 28.8 pmol/L. After an additional four days, both FT4 and FT3 levels decreased. Through this period, no thyrotoxic symptom or physical sign had appeared. We also measured FT4 and FT3 levels in her cryopreserved serum by ultrafiltration LC-MS/MS. Her FT4 level measured by ultrafiltration LC-MS/MS on the visiting day and two days later were 160.0 and 135.5 pmol/L, respectively, indicating that the toxic dose of levothyroxine was partly changed to T3 during the two days. The FT3/FT4 ratios were revealed to be low, accounting for the patient’s benign clinical course despite temporal toxic exposure to levothyroxine. It is implied that prior discontinuation of supplementary levothyroxine increases potential vacant binding sites for thyroid hormone as a buffer to prevent toxic T3 effect.
Conclusion: It was helpful to clarify the time dependent changes in free thyroid hormone levels by ultrafiltration LC-MS/MS in discussing the clinical course in this case. Though mass spectrometry has a disadvantage in speed for routine laboratory use, its accurate measurement, particularly of levels exceeding the measurable range of the immunoassay, provides valuable information for more appropriate management of extreme thyrotoxicosis.
Effect of Corneal Cross-linking on Endothelial Cell Density and Morphology in the Peripheral Cornea.
Authors: Goukon Hiroyasu , Kamiya Kazutaka , Takahashi Masahide , Shoji Nobuyuki 
Published: March 2020

Abstract
BACKGROUND: To compare the endothelial cell density and morphology in the peripheral cornea before and after corneal cross-linking (CXL).METHODS: This study evaluated thirty-one eyes of 31 patients who were treated with standard CXL for progressive keratoconus. Preoperatively and 6 months postoperatively, we compared the corneal endothelial cell density (ECD), the coefficient of variation in cell size (CV), and the percentage of hexagonal cells (HEX), in the peripheral regions of the cornea, using a non-contact specular microscope (EM-3000, Tomey).RESULTS: All keratoconic eyes in this series were measurable in the peripheral regions. No significant differences were found in the peripheral ECD preoperatively and 6 months postoperatively at each point (Wilcoxon signed-rank test, superior, p=0.16, nasal superior, p=0.12, temporal superior, p= 0.17, inferior, p=0.37, nasal inferior, p=0.28, temporal inferior, p=0.17). The mean percentage of the ECD loss was 1.3%, 1.3%, 1.0%, 1.4%, 0.7%, and 1.4%, respectively. No significant differences in the peripheral CV or HEX were found preoperatively and 6 months postoperatively at each point.CONCLUSIONS: Standard CXL does not cause significant changes in endothelial cell density, polymegethism, or polymorphism, in the peripheral regions of the cornea. It is suggested that CXL is a minimally invasive surgical approach for progressive keratoconus, even in terms of peripheral endothelial cells.