bluuebunny/crossref_metadata_2025_split huggingface dataset:
Novel TRPV6 mutations in the spectrum of transient neonatal hyperparathyroidism
Authors: Suzuki Yoshiro , Sawada Hirotake , Tokumasu Tomoko , Suzuki Shigeru , Ninomiya Shinsuke , Shirai Masaru , Mukai Tokuo , Saito Claire T. , Nishimura Gen , Tominaga Makoto 
Published: July 2020

AbstractMaternal–fetal calcium (Ca2+) transport in the placenta plays a critical role in maintaining fetal bone mineralization. Mutations in the gene encoding the transient receptor potential cation channel, subfamily V, member 6 (TRPV6) have been identified as causative mutations of transient neonatal hyperparathyroidism due to insufficient maternal–fetal Ca2+ transport in the placenta. In this study, we found two novel mutations in subjects that have transient neonatal hyperparathyroidism. TRPV6 carrying the mutation p.Arg390His that localizes to the outer edge of the first transmembrane domain (S1) showed impaired trafficking to the plasma membrane, whereas TRPV6 having the mutation p.Gly291Ser in the sixth ankyrin repeat (AR) domain had channel properties that were comparable those of WT channels, although the increases in steady-state intracellular Ca2+ concentration could have led to Ca2+ overload and subsequent death of cells expressing this mutant channel. These results indicate that the AR6 domain contributes to TRPV6-mediated maintenance of intracellular Ca2+ concentrations, and that this region could play a novel role in regulating the activity of TRPV6 Ca2+-selective channels.
Efficacy of phage cocktail AB-SA01 therapy in diabetic mouse wound infections caused by multidrug-resistant Staphylococcus aureus
Authors: Kifelew Legesse Garedew , Warner Morgyn S. , Morales Sandra , Vaughan Lewis , Woodman Richard , Fitridge Robert , Mitchell James G. , Speck Peter 
Published: July 2020

AbstractBackgroundDiabetic foot ulcer (DFU) is a serious complication of diabetes mellitus. Antibiotic-resistantStaphylococcus aureusis frequently isolated from DFU infections. Bacteriophages (phages) represent an alternative or adjunct treatment to antibiotic therapy. Here we describe the efficacy of AB-SA01, a cocktail of threeS. aureus Myoviridaephages, made to current good manufacturing practice (cGMP) standards, and which has undergone two phase I clinical trials, in treatment of multidrug-resistant (MDR)S. aureusinfections.ResultsWounds of saline-treated mice showed no healing, but expanded and became inflamed, ulcerated, and suppurating. In contrast, AB-SA01 treatment decreased the bacterial load with efficacy similar or superior to vancomycin treatment. At the end of the treatment period, there was a significant decrease (p < 0.001) in bacterial load and wound size in infected phage- and vancomycin-treated groups compared with infected saline-treated mice. In phage-treated mice, wound healing was seen similar to vancomycin treatment. No mortality was recorded associated with infections, and post-mortem examinations did not show any evident pathological lesions other than the skin wounds. No adverse effects related to the application of phages were observed.ConclusionTopical application of phage cocktail AB-SA01 is effective, as shown by bacterial load reduction and wound closure, in the treatment of diabetic wound infections caused by MDRS. aureus. Our results suggest that topical phage cocktail treatment may be effective in treating antibiotic-resistantS. aureusDFU infections.
Participants who were difficult to recruit at baseline are less likely to complete a follow-up questionnaire – results from the German National Cohort
Authors: Rach Stefan , Günther Kathrin , Hadeler Birte 
Published: July 2020

Abstract
Background
With declining response proportions in population-based research the importance of evaluating the effectiveness of measures aimed at improving response increases. We investigated whether an additional flyer with information about the study influences participation in a follow-up questionnaire and the time participants take to send back filled questionnaire.

Methods
In a trial embedded within the German National Cohort we compared responses to invitations for a follow-up questionnaire either including a flyer with information about the cohort study or not including it. Outcomes of interest were participation in the follow-up (yes vs. no) and time to response (in days). We analyzed paradata from baseline recruitment to account for differences in recruitment history between participants.

Results
Adding a flyer to invitations did neither influence the likelihood of participation in the follow-up (OR 0.94, 95% CI: 0.80, 1.11), nor the time it took participants to return completed questionnaires (β̂ = 1.71, 95% CI: − 1.01, 4.44). Subjects who, at baseline, needed to be reminded before eventually participating in examinations and subjects who scheduled three or more appointments until eventually completing baseline examinations were less likely to complete the follow-up questionnaire and, if they did, took more time to complete questionnaires.

Conclusions
Evaluating the effectiveness of measures aimed at increasing response can help to improve the allocation of usually limited resources. Characteristics of baseline recruitment can influence response to follow-up studies and therefore information about recruitment history (i.e., paradata) might prove useful to tailor follow-up recruitments to those who were difficult to recruit during baseline. To this end, however, it is necessary to routinely and meticulously collect paradata during recruitment.
APOE – a genetic marker of comorbidity in subjects with morbid obesity
Authors: Farup Per G. , Rootwelt Helge , Hestad Knut 
Published: July 2020

Abstract
Background
In population-based studies, the genetic variability of the APOE E alleles have been associated with health outcomes. Health problems are common in subjects with obesity. This study explored associations between the APOE E alleles and comorbidity in subjects with morbid obesity.

Methods
The study included consecutive subjects referred for evaluation of bariatric surgery with morbid obesity (defined as BMI > 40 or > 35 kg/m2 with complications related to obesity). The subjects followed a conservative weight loss program for 6 months before surgery and had a follow-up visit 12 months after surgery. Demographic data and a set psychosomatic scores (musculoskeletal pain, WHO-5 Well-Being Index, Rosenberg Self-Esteem Scale, Hopkins Symptom Check-list 10; Epworth Sleepiness Scale, and Fatigue Severity Scale) were collected, and blood samples were analysed for haematological and biochemical parameters and APOE alleles.

Results
One hundred and forty subjects (men/women: 32 (23%)/108 (77%) with mean age 43.0 (SD 8.7) years and BMI 42.1 (SD 3.8) kg/m2 were included. One hundred and eight and 92 subjects had data after conservative treatment and 12 months after surgery, respectively. The prevalence of the APOE alleles were: E2E2: 1 (0.7%), E2E3: 13 (9.3%), E2E4: 4 (2.9%), E3E3: 71 (50.7%), E3E4: 47 (33.6%), and E4E4: 4 (2.9%). The prevalence rates were as anticipated in a Norwegian population. The weight loss during conservative treatment and after bariatric surgery was independent of E allele variability. E2 was associated with a significant or clear trend toward improvement of all psychosomatic disorders. There was a significant fall in CRP during the two treatment periods with weight loss. E2 and E4 were significantly associated with high and low CRP, respectively, but no associations were seen between CRP and comorbidity.

Conclusions
The most marked finding was the association between E2 and improvement of all psychosomatic disorders. The positive and negative associations between CRP and E2 and E4, respectively, could indicate effects on inflammation and immunological reactions.
Study protocol for an open-label, single-arm, phase Ib/II study of combination of toripalimab, nab-paclitaxel, and gemcitabine as the first-line treatment for patients with unresectable pancreatic ductal adenocarcinoma
Authors: Shui Lin , Cheng Ke , Li Xiaofen , Shui Pixian , Zhou Xiaohan , Li Jian , Yi Cheng , Cao Dan 
Published: July 2020

Abstract
Background
Pancreatic ductal adenocarcinoma (PDAC) is a fatal disease with a dismal response to single-use of immune checkpoint inhibitors (ICIs). ICIs combined with systemic therapy has shown efficacy and safety in various solid tumors. Nab-paclitaxel and gemcitabine (AG), as the standard first-line treatment for advanced PDAC, has been widely used in recent years. The combination of ICIs and AG chemotherapy appears to be a promising option in the treatment of PDAC.

Methods
This is an open-label, single-arm, and single-center phase Ib/II trial. The enrolled subjects are the unresectable (locally advanced or metastatic) PDAC patients without previous systemic treatments. All subjects receive an intravenous injection of gemcitabine 1000 mg/m2 and nab-paclitaxel 125 mg/m2 on day 1 and day 8, along with toripalimab 240 mg at day 1 every 3 weeks. The subjects may discontinue the treatment because of progression disease (PD), intolerable toxicities, requirements of patients or researchers. For local advanced patients who are evaluated as partial response (PR), surgeons need to assess the surgical possibility. The primary objective of this trial is to evaluate the safety and overall survival (OS) of this combination therapy; and the secondary objective is related to the assessment of objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and the rate of resection or R0 resection after receiving toripalimab plus AG treatment. Besides, we expect to identify the predictive biomarkers (such as MMR protein and PD-L1 expression, the number of TILs, the small RNA of EBV and so on) and explore the correlation between these biomarkers and tumor response to this combined regimen.

Discussion
This trial is the first attempt to evaluate the efficacy and safety of the combination of toripalimab plus AG chemotherapy as a first-line treatment for unresectable PDAC patients. The results of this phase Ib/II study will provide preliminary evidence for further assessment of this combined therapeutic regimen for unresectable PDAC patients.

Trial registration
Trial registration: ChiCTR (ChiCTR2000032293). Registered 25 April 2020 - Retrospectively registered.
Unilateral multifocal choroiditis following EBV-positive mononucleosis responsive to immunosuppression: a case report
Authors: Borkar P. P. , Grassi M. A. 
Published: July 2020

Abstract
Background
Multifocal choroiditis (MFC) is a relatively uncommon bilateral inflammatory chorioretinopathy affecting Caucasian young women with myopia. We present images from a case of completely unilateral multifocal choroiditis following EBV-positive mononucleosis that demonstrated a dramatic clinical response to immunosuppression.

Case presentation
A 20-year-old woman with bilateral high myopia (−6D) and a documented normal prior retinal examination presented with visual loss in the right eye 2 months following confirmed Epstein-Barr virus (EBV) positive mononucleosis. Ophthalmoscopic examination showed completely unilateral placoid lesions of variable age. The left eye was unaffected. Fluorescein angiography revealed active leakage, especially in the parafovea. Spectral domain optical coherence tomography (SD-OCT) demonstrated sub-retinal pigment epithelial nodular deposits, some of which were confluent with overlying intra-retinal fluid and indistinct margins. Upon treatment with the immunosuppressant azathioprine there was significant resolution of the lesions in her right eye along with improvement in vision.

Conclusion
This is a rare case of completely unilateral MFC following an episode of EBV positive mononucleosis that showed a dramatic response to immunosuppression.
Impact of substandard and falsified antimalarials in Zambia: application of the SAFARI model
Authors: Jackson Kathryn D. , Higgins Colleen R. , Laing Sarah K. , Mwila Chiluba , Kobayashi Tamaki , Ippolito Matthew M. , Sylvia Sean , Ozawa Sachiko 
Published: July 2020

Abstract
Background
Many countries are striving to become malaria-free, but global reduction in case estimates has stagnated in recent years. Substandard and falsified medicines may contribute to this lack of progress. Zambia aims to eliminate their annual burden of 1.2 million pediatric malaria cases and 2500 child deaths due to malaria. We examined the health and economic impact of poor-quality antimalarials in Zambia.

Methods
An agent-based model, Substandard and Falsified Antimalarial Research Impact (SAFARI), was modified and applied to Zambia. The model was developed to simulate population characteristics, malaria incidence, patient care-seeking, disease progression, treatment outcomes, and associated costs of malaria for children under age five. Zambia-specific demographic, epidemiological, and cost inputs were extracted from the literature. Simulations were run to estimate the health and economic impact of poor-quality antimalarials, the effect of potential artemisinin resistance, and six additional malaria focused policy interventions.

Results
We simulated annual malaria cases among Zambian children under five. At baseline, we found 2610 deaths resulting in $141.5 million in annual economic burden of malaria. We estimated that elimination of substandard and falsified antimalarials would result in an 8.1% (n = 213) reduction in under-five deaths, prevent 937 hospitalizations, and realize $8.5 million in economic savings, annually. Potential artemisinin resistance could further increase deaths by 6.3% (n = 166) and cost an additional $9.7 million every year.

Conclusions
Eliminating substandard and falsified antimalarials is an important step towards a malaria-free Zambia. Beyond the dissemination of insecticide-treated bed nets, indoor residual spraying, and other malaria control measures, attention must also be paid to assure the quality of antimalarial treatments.
Acceptability of a hypothetical preventative HIV vaccine among people who use drugs in Vancouver, Canada
Authors: Fleming Taylor , Valleriani Jenna , Ng Cara , Maher Lisa , Small Will , McNeil Ryan 
Published: July 2020

Abstract
Background
As research on HIV vaccines continues to advance, studies exploring the feasibility of this intervention are necessary to inform uptake and dissemination strategies with key populations, including people who use drugs (PWUD).

Methods
We conducted 25 in-depth qualitative interviews examining HIV vaccine acceptability among PWUD in Vancouver, Canada. Participants were recruited from an ongoing prospective cohort of HIV-negative PWUD. Data were coded using NVivo, and analyzed thematically.

Results
Acceptability was framed by practical considerations such as cost and side effects, and was influenced by broader trust of government bodies and health care professionals. While an HIV vaccine was perceived as an important prevention tool, willingness to be vaccinated was low. Results suggest that future vaccine implementation must consider how to minimize the burden an HIV vaccine may place on PWUD. Centering the role of health care providers in information dissemination and delivery may assist with uptake.

Conclusions
Our findings suggest improvements in care and improved patient-provider relationships would increase the acceptability of a potential HIV vaccine among this population.
Bilobalide protects against ischemia/reperfusion-induced oxidative stress and inflammatory responses via the MAPK/NF-κB pathways in rats
Authors: Li Ying , Jiang Jiliang , Tong Liangcheng , Gao Tingting , Bai Lei , Xue Qing , Xing Jianxin , Wang Qin , Lyu Haoran , Cai Min , Sun Zhongyang 
Published: July 2020

AbstractBackgroundClinically, skeletal muscle ischemia/reperfusion injury is a life-threatening syndrome that is often caused by skeletal muscle damage and is characterized by oxidative stress and inflammatory responses. Bilobalide has been found to have antioxidative and anti-inflammatory effects. However, it is unclear whether bilobalide can protect skeletal muscle from ischemia/reperfusion injury.MethodsThe effects of bilobalide on ischemia/reperfusion-injured skeletal muscle were investigated by performing hematoxylin and eosin staining and assessing the wet weight/dry weight ratio of muscle tissue. Then, we measured lipid peroxidation, antioxidant activity and inflammatory cytokine levels. Moreover, Western blotting was conducted to examine the protein levels of MAPK/NF-κB pathway members.ResultsBilobalide treatment could protected hind limb skeletal muscle from ischemia/reperfusion injury by alleviating oxidative stress and inflammatory responses via the MAPK/NF-κB pathways.ConclusionsBilobalide may be a promising drug for I/R-injured muscle tissue. However, the specific mechanisms for the protective effects still need further study.
Molecular detection of Bartonella in ixodid ticks collected from yaks and plateau pikas (Ochotona curzoniae) in Shiqu County, China
Authors: Hao Lili , Yuan Dongbo , Guo Li , Hou Wei , Mo Xi , Yin Jie , Yang Aiguo , Li Rui 
Published: July 2020

Abstract
Background
Bartonella bacteria have been associated with an increasingly wide range of human and animal diseases. These emerging pathogens have been identified as being globally dispersed. Ticks and small rodents are known hosts of Bartonella and play a significant role in the preservation and circulation of Bartonella in nature. This study investigated the occurrence of hoist spp. in ticks (Acari: Ixodidae) and plateau pikas (Ochotona curzoniae) in Shiqu County, which is located on the eastern Qinghai-Tibetan Plateau in China. Shiqu County is spread over approximately 26,000 km2, with an average altitude of above 4200 m and a vast area of pastureland.

Results
A total of 818 ticks (Dermacentor everestianus, 79.0%, 646/818; Haemaphysalis qinghaiensis, 21.0%, 172/818) were collected from yaks in 4 villages of Shiqu County. Only Bartonella melophagi was detected in tick samples, with a total prevalence of 30.1% (246/818). The infection rates of B. melophagi in ticks from Arizha, Maga, Derongma, and Changxgma were 4.8, 76.8, 12.5, and 18.0%, respectively. The infection rate of B. melophagi in Maga was higher (p < 0.01) than those in other villages. Regarding plateau pikas, the total infection rate of Bartonella spp. was 21.7% (62/286), with 16.7% (12/72), 30.9% (25/81), 13.8% (9/65), and 23.5% (16/68) in Arizha, Maga, Derongma, and Changxgma, respectively. Finally, B. queenslandensis and B. grahamii were detected in plateau pika. No significant difference was observed (p > 0.05) in the infection rates between these study sites.

Conclusion
To date, only D. everestianus and H. qinghaiensis were found in Shiqu County with high infection of Bartonella spp. in the ticks and plateau pika. The threats of Bartonella species to public health should be closely monitored.
Lipoprotein (a) predicts recurrent worse outcomes in type 2 diabetes mellitus patients with prior cardiovascular events: a prospective, observational cohort study
Authors: Zhang Yan , Jin Jing-Lu , Cao Ye-Xuan , Zhang Hui-Wen , Guo Yuan-Lin , Wu Na-Qiong , Zhu Cheng-Gang , Gao Ying , Hua Qi , Li Yan-Fang , Xu Rui-Xia , Li Jian-Jun 
Published: July 2020

Abstract
Background
Merging studies have reported the association of lipoprotein(a) [Lp(a)] with poor outcomes of coronary artery disease (CAD) in patients with type 2 diabetes mellitus (T2DM). However, the prognostic importance of Lp(a) for recurrent cardiovascular events (CVEs) is currently undetermined in patients with T2DM and prior CVEs.

Methods
From April 2011 to March 2017, we consecutively recruited 2284 T2DM patients with prior CVEs. Patients were categorized into low, medium, and high groups by Lp(a) levels and followed up for recurrent CVEs, including nonfatal acute myocardial infarction, stroke, and cardiovascular mortality. Kaplan–Meier, Cox regression and C-statistic analyses were performed.

Results
During 7613 patient-years’ follow-up, 153 recurrent CVEs occurred. Lp(a) levels were significantly higher in patients with recurrent CVEs than counterparts (20.44 vs. 14.71 mg/dL, p = 0.002). Kaplan–Meier analysis revealed that the event-free survival rate was dramatically lower in high and medium Lp(a) groups than that in low group irrespective of HBA1c status (< 7.0%; ≥ 7.0%, both p < 0.05). Furthermore, multivariate Cox regression models indicated that Lp(a) was independently associated with high risk of recurrent CVEs [HR(95% CI): 2.049 (1.308–3.212)], such data remains in different HBA1c status (HR(95% CI): < 7.0%, 2.009 (1.051–3.840); ≥ 7.0%, 2.162 (1.148–4.073)). Moreover, the results of C-statistic were significantly improved by 0.029 when added Lp(a) to the Cox model.

Conclusions
Our data, for the first time, confirmed that Lp(a) was an independent predictor for recurrent CVEs in T2DM patients with prior CVEs, suggesting that Lp(a) measurement may help to further risk stratification for T2DM patients after they suffered a first CVE.
miR-138-5p inhibits the malignant progression of prostate cancer by targeting FOXC1
Authors: Zhang Dapeng , Liu Xiaodong , Zhang Qingwei , Chen Xin 
Published: July 2020

Abstract
Background
This study aimed to uncover the effect of miR-138-5p on the proliferation and metastasis of PCa cell lines, and further explore the potential regulatory mechanisms via regulating FOXC1.

Methods
60 pairs cancer tissues and corresponding paracancerous ones from PCa patients were collected to assess the expression level of miR-138-5p by qRT-PCR. Subsequently, over-expression of miR-138-5p were established to explore the proliferation and metastasis of miR-138-5p in PCa cell lines was analyzed by CCK-8, Transwell assay and Wounding healing assay, respectively. Bioinformatics analysis and luciferase reporter gene assay were performed to search for the target genes of miR-138-5p, and FOXC1 was selected. Finally, the biological role of miR-138-5p and FOXC1 in the progression of PCa was clarified by a series of rescue experiments.

Results
The results of qRT-PCR revealed that miR-138-5p was lowly expressed in PCa tissues and cell lines. Besides, the PCa patients with low-miR-138-5p had a high Gleason score, lymph node metastasis and poor prognosis of PCa, compared with these patients with high-miR-138-5p. Over-expression of miR-138-5p inhibited the proliferative, migratory and invasive capacities of PC-3 and DU-145 cells. Bioinformatics analysis and luciferase reporter gene assay suggested that FOXC1 was predicted to be the target gene of miR-138-5p. Moreover, FOXC1 expression level was negatively correlated to that of miR-138-5p in PCa tissues. Importantly, over-expression of FOXC1 could reverse miR-138-5p mimic induced-inhibition of PCa malignant progression.

Conclusions
Downregulated miR-138-5p was closely associated with high Gleason score, more lymph node metastasis and poor prognosis of PCa patients. In addition, miR-138-5p alleviated the malignant progression of PCa by targeting and downregulating FOXC1.