bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical and molecular basis of hepatocerebral mitochondrial DNA depletion syndrome in Japan: Evaluation of outcomes after liver transplantation
Authors: Shimura Masaru , Kuranobu Naomi , Ogawa-Tominaga Minako , Akiyama Nana , Sugiyama Yohei , Ebihara Tomohiro , Fushimi Takuya , Ichimoto Keiko , Matsunaga Ayako , Tsuruoka Tomoko , Kishita Yoshihito , Umetsu Shuichiro , Inui Ayano , Fujisawa Tomoo , Tanikawa Ken , Ito Reiko , Fukuda Akinari , Murakami Jun , Kaji Shunsaku , Kasahara Mureo , Shiraki Kazuo , Ohtake Akira , Okazaki Yasushi , Murayama Kei
Published: June 2020

Background Hepatocerebral mitochondrial DNA depletion syndrome (MTDPS) is a disease caused by defects in mitochondrial DNA maintenance and leads to liver failure and neurological complications during infancy. Liver transplantation (LT) remains controversial due to poor outcomes associated with extrahepatic symptoms. The purposes of this study were to clarify the current clinical and molecular features of hepatocerebral MTDPS and to evaluate the outcomes of LT in MTDPS patients in Japan.Results We retrospectively assessed the clinical and genetic findings, as well as the clinical courses, of 23 hepatocerebral MTDPS patients from a pool of 999 patients who were diagnosed with mitochondrial diseases between 2007 and 2019. Causative genes were identified in 19 of 23 patients: MPV17 (n = 13), DGUOK (n = 3), POLG (n = 1), and MICOS13 (n = 1). Eight MPV17-deficient patients harbored c.451dupC and all three DGUOK-deficient patients harbored c.143-307_170del335. The most common initial manifestation was failure to thrive (n = 13, 56.5%). The most frequent liver symptom was cholestasis (n = 21, 91.3%). LT was performed on 12 patients, including nine MPV17-deficient and two DGUOK-deficient patients. Among the 12 transplanted patients, five, including one with mild intellectual disability, survived; while seven who had remarkable neurological symptoms before LT died. Five of the MPV17-deficient survivors had either c.149G>A or c.293C>T. Conclusions MPV17 was the most common genetic cause of hepatocerebral MTDPS. The outcome of LT for MTDPS was not favorable, as previously reported, however, patients harboring MPV17 mutations associated with mild phenotypes such as c.149G>A or c.293C>T, and exhibiting no marked neurologic manifestations before LT, had a better prognosis after LT.
How do parents deal with their children's chronic kidney disease? A qualitative study for identifying factors related to parent's adaptation
Authors: Khorsandi Fatemeh , Parizad Naser , Feizi Aram , maslakpak Masumeh Hemmati
Published: June 2020

Background: Parents’ adaptation affects the health outcomes of children with chronic kidney diseases (CKD). Identifying factors that affect parents’ adaptation is necessary to understand their adaptation status. This study aims to explore factors related to the adaptation of parents who have children with CKD. Methods: This was a qualitative study with a content analysis approach. Seventeen parents of children with CKD were selected by using purposive sampling. One of the researchers performed semi-structured, in-depth, face-to-face interviews to collect data. Conventional content analysis was used to analyze data. Results: Two main categories extracted from the data were “adaptation facilitators” and “adaptation barriers.” Adaptation facilitators supported by three sub-categories: “social support,” “family capability,” “spiritual beliefs.” Four sub-categories of “adaptation barriers” were revealed as follows: “family-related barrier,” “mental stress by others,” “the chronic nature of the disease,” and “unfavorable treatment conditions.” Conclusions: Identifying the factors influencing parental adaptation helps the medical staff to make the necessary interventions to support the parents. According to this study, increasing parent access to the required information, supporting them financially and emotionally, and helping them identify support resources can facilitate their adaptation to their child's chronic illness. Also, identifying and eliminating adaptation barriers can help parents deal better with their child’s chronic disease.
Microparticles derived from human erythropoietin mRNA-transfected mesenchymal stem cells inhibit epithelial-to-mesenchymal transition and ameliorate renal interstitial fibrosis
Authors: Lee Mirae , Kim Seok-hyung , Jhee Jong Hyun , Kim Tae Yeon , Choi Hoon Young , Kim Hyung Jong , Park Hyeong Cheon
Published: June 2020

Background: Renal tubulointerstitial fibrosis (TIF) plays an important role in the progression of chronic kidney disease (CKD) and its pathogenesis involves epithelial-to-mesenchymal transition (EMT) upon renal injury. Recombinant human erythropoietin (rhEPO) has been shown to display novel cytoprotective effects, in part by inhibiting transforming growth factor (TGF)-β1-induced EMT. Here, we evaluated the inhibitory effects of microparticles (MPs) derived from human EPO gene-transfected kidney mesenchymal stem cells (hEPO-KMSCs) against TGF-β1-induced EMT in Madin-Darby canine kidney (MDCK) cells and against TIF in mouse kidneys with unilateral ureteral obstruction (UUO).Methods: EMT was induced in MDCK cells by treatment with TGF-β1 (5 ng/mL) for 48 h and then inhibited by co-treatment with rhEPO (100 IU/mL), mock gene-transfected KMSC-derived MPs (MOCK-MPs), or hEPO-KMSC-derived MPs (hEPO-MPs) for a further 48 h. UUO was induced in FVB/N mice, which were then treated with rhEPO (1000 IU/kg, intraperitoneally, every other day for 1 week), MOCK-MPs, or hEPO-MPs (80 mg, intravenously). Alpha-smooth muscle actin (α-SMA), fibronectin, and E-cadherin expression were evaluated in MDCK cells and kidney tissues, and the extent of TIF in UUO kidneys was assessed by immunohistochemical staining.Results: TGF-β1 treatment significantly increased α-SMA and fibronectin expression in MDCK cells and decreased that of E-cadherin, while co-treatment with rhEPO, MOCK-MPs, or hEPO-MPs markedly attenuated these changes. In addition, rhEPO and hEPO-MP treatment effectively decreased phosphorylated Smad2 and Smad3, as well as phosphorylated p38 mitogen-activated protein kinase (MAPK) expression, suggesting that rhEPO and rhEPO-MPs can inhibit TGF-β1-induced EMT via both Smad and non-Smad pathways. rhEPO and hEPO-MP treatment also significantly attenuated the extent of renal TIF after one week of UUO compared to MOCK-MPs, with hEPO-MPs significantly reducing myofibroblast and F4/80+ macrophage infiltration as well as EMT marker expression in UUO renal tissues in a similar manner to rhEPO. Conclusions: Our results demonstrate that hEPO-MPs modulate TGF-β1-induced EMT in MDCK cells via the Smad2, Smad3, and p38 MAPK pathways and significantly attenuated renal TIF in UUO kidneys.
Validation of depressive symptoms, social support, and minority stress scales among Gay, Bisexual, and other men who have with men (GBMSM) in Nigeria, Africa: A Mixed Methods Approach
Authors: Ogunbajo Adedotun , Iwuagwu Stella , Williams Rashidi , Biello Katie B , Kahler Christopher W , Sandfort Theodorus , Mimiaga Matthew J
Published: June 2020

Background: Gay, bisexual, and other men who have sex with men (GBMSM) in Nigeria experience social marginalization, discrimination and violence due to their sexual identity, which may negatively impact physical, mental, and sexual health outcomes. Studies on GBMSM in Africa utilize measurement scales developed largely for populations in the Global North. The validity and reliability of these instruments—to our knowledge—have never been thoroughly investigated among GBMSM in Nigeria. The aim of the current study was to determine the validity and reliability of the English versions of the Center for Epidemiologic Studies Depression Scale (CESD-R), Multidimensional Scale of Perceived Social Support (MSPSS), and LGBT Minority Stress Measure among a large multi-state sample of GBMSM Nigeria.Methods: Between January and June 2019, we conducted cognitive interviews (N=30) and quantitative assessments (N=406) with GBMSM in Nigeria. The cognitive interviews assessed comprehension of scale items and elicited suggestions for scale modifications. The quantitative assessment was used to gather psychosocial health data and to evaluate psychometric properties and construct validity of the modified scales. We utilized confirmatory factor analysis to assess factor structure, correlation coefficients, and Cronbach’s alpha to examine scale validity and internal consistency. Results: Based on participant feedback from the cognitive interviews, we made slight modifications (i.e., culturally appropriate word substitutions) to all three scales. Results of quantitative analyses indicated good psychometric properties including high factor loadings, internal consistency and construct validity among the CESD-R, MSPSS, and LGBT Minority Stress Measure among GBMSM in Nigeria. Conclusion: These results suggests that modifying research scales to be more culturally relevant likely do not jeopardize their validity and reliability. We found that modified scales measuring depressive symptoms, perceived social support, and minority stress among GBMSM in Nigeria remained valid. More research is needed to explore whether the psychometric properties remain if the scales are translated into broken English (Pidgin) and other traditional Nigerian languages (Yoruba, Igbo and Hausa).
Enzymatic activity and brine shrimp lethality of venom from the large brown spitting cobra (Naja ashei) and its neutralization by antivenom
Authors: Okumu Mitchel Otieno , Mbaria James Mucunu , Gikunju Joseph Kangangi , Mbuthia Paul Gichohi , Madadi Vincent Odongo , Ochola Francis Okumu
Published: June 2020

Objective: Naja ashei is a snake of medical importance in Kenya, Ethiopia, Somalia, Uganda, and Tanzania. Little is known about the enzymatic (snake venom phospholipases A2; svPLA2’s) and toxic (lethal) activities of Naja ashei venom and crucially, the safety and capacity of available antivenom to neutralize these effects. This study aimed to determine the enzymatic and toxic activities of Naja ashei venom and the capacity of Indian and Mexican manufactured antivenoms to neutralize these effects. The protein content of the venom and the test antivenoms were also evaluated. A 12-point log concentration-response curve (0.5-22.5 µg/mL) was generated on an agarose-egg yolk model to predict the svPLA2 activity of the venom. The toxicity profile of the venom and antivenoms was evaluated in the brine shrimp lethality assay. Lowry’s method was used for protein estimation. Results: Low and intermediate concentrations of the venom exhibited similar svPLA2 activities. The same was true for concentrations >15µg/mL. Intermediate and high doses of the venom exhibited similar mortalities in brine shrimp and test antivenoms were generally non-toxic but poorly neutralized svPLA2 activity. Mexican manufactured antivenom had lower protein content but neutralized venom-induced brine shrimp lethality much more effectively than Indian manufactured antivenom.
Are supplemental appraisal/reimbursement processes needed for rare disease treatments? An international comparison of country approaches
Authors: Nicod Elena , Whittal Amanda , Drummond Michael , Facey Karen
Published: June 2020

BACKGROUND There is increasing recognition that conventional appraisal approaches may be unsuitable for assessing the value rare disease treatments (RDTs). This research examines what supplemental appraisal/reimbursement processes for RDTs are used internationally and how they can be characterised. A qualitative research design was used that included (1) documentation of country appraisal/reimbursement processes for RDTs via questionnaires, desk research and iterative interactions with country experts to produce country vignettes, and (2) a cross-country analysis of these processes to identify and characterise features in supplemental processes for RDTs, and compare them to countries without supplemental processes. RESULTS Thirty-two of the 37 invited countries participated in this research. Forty-one percent (13/32) use supplemental processes for RDTs. Their level of integration within standard processes ranged from low to high, characterised by whether they are separate or partially separate from the standard process, adapted or accelerated standard processes, or standard processes that may be applied to RDTs. They are characterised by features implemented throughout the appraisal process. These features are mechanisms that allow application of different standards to assess the value of the medicine, support to the appraisal/decision-making process, overcome the issues of lack of cost-effectiveness, or exempt from part of/the full appraisal/reimbursement process. They increase the likelihood of reimbursement by adjusting and/or foregoing part of the assessment process, or accepting to pay more for the same added benefit as for common conditions. A large proportion of countries with standard processes include one or more of these features (formally or informally) or are discussing potential changes in their systems. CONCLUSIONS Results suggest revealed preferences to treat RDTs differently than conventional medicines. Some of the challenges around uncertainty and high price remain, but supplemental process features can support decision-making that is more flexible and consistent. Many of these processes are new and countries continue to adjust as they gain experience.
How to choose kinematic or mechanical alignment individually according to preoperative characteristics of patients?
Authors: Luan Chong , Xu Dong-Tan , Chen Ning-Jie , Wang Fei-Fei , Tian Kang- Song , Wei Chao , Wang Xian-Bin
Published: June 2020

Background Making decisions in alignment techniques in total knee arthroplasty (TKA) remains controversial. This study aims to identify the potential patients who were suitable for the kinematic (KA) or mechanical alignment (MA). Methods We reviewed 296 consecutive patients (296 TKAs, including 114 KA-TKAs and 182 MA-TKAs) who underwent unilateral TKA using a computer-assisted navigation from 2016 to 2018 in our prospectively maintained database. The minimum followup was one year. Clinical outcomes including the range of motion (ROM) and knee society score (KSS) were compared between KA-TKAs and MA-TKAs. Multiple regression models were used to evaluate the relationship between alignment techniques and KSS at the 1-year followup. Interaction and stratified analyses were conducted according to gender, age, body mass index (BMI), preoperative hip-knee-ankle (HKA) angle, ROM and KSS.Results ROM and KSS at the 1-year followup didn't differ between MA-TKAs and KA-TKAs (all p>0.05). Alignment techniques did not associate with postoperative ROM (Adjusted β=0.4, 95% confidence interval [CI]: -0.3, 1.6; p=0.752) or 1-year KSS (Adjusted β=2.2, 95%CI: -0.7, 5.6; p=0.107). Patients with a BMI more than 30 kg/m^2 achieved better 1-year KSS when using MA than KA (p for interaction<0.05). Additionally, patients with preoperative HKA angle more than 10 degrees varus benefited more from KA than MA (p for interaction<0.05).Conclusions Patients with severe varus deformity may be suitable for the KA technique, whereas MA should be used in obese patients.
Predictive Value of the Surgical Apgar Score on Postoperative Complications in Advanced Gastric Cancer Patients Treated with Neoadjuvant Chemotherapy Followed by Radical Gastrectomy: A Single Center Retrospective Study
Authors: Hayashi Masato , Yoshikawa Takaki , Yura Masahiro , Otsuki Sho , Yamagata Yukinori , Morita Shinji , Katai Hitoshi , Nishida Toshirou
Published: June 2020

Background: The surgical Apgar score (SAS) or modified SAS (mSAS) has been reported as a simple and easy risk assessment system to predict postoperative complications (PCs) in primary surgery for gastric cancer (GC). However, there are still few studies which revealed the SAS’s utility in gastric surgery after neoadjuvant chemotherapy (NAC). Methods: One hundred and fifteen patients who received NAC and R0 gastrectomy from 2008 and 2015 were included in this study. The SAS was determined by estimated blood loss (EBL), lowest intraoperative mean arterial pressure (LMAP), and lowest heat rate (LHR). The mSAS was determined by the EBL reassessed using the interquartile values. The predictive values of the SAS/mSAS for PCs were assessed with uni and multivariate analyses. Results: Among 115 patients, 41 (35.7%) developed PCs. According to analyses with receiver operating characteristic (ROC) curve of the SAS and mSAS for predicting PCs, the cutoff value of the mSAS was set at 8. The rates of anastomotic leakage, pancreatic fistula, and arrhythmia in patients with high mSAS ( > 8) values were higher, compared to those with low (0-3) and moderate (4-7) mSAS values. A multiple logistic regression analysis detected operation time, Body Mass Index (BMI), and Diabetes Mellitus (DM) were independent risk factors for PCs. The mSAS was not a significant predictor. Conclusions: Neither the SAS nor mSAS was a useful predictor of PCs in patients treated with NAC followed by radical gastrectomy. The predictive value of SAS/mSAS is limited in patients undergoing surgery after NAC.
Validation of a point-of-care capillary lactate measuring device (Lactate Pro 2).
Authors: Raa Anette , Sunde Geir Arne , Bolann Bjørn , Kvåle Reidar , Bjerkvig Christopher , Eliassen Håkon Skogrand , Wentzel-Larsen Tore , Heltne Jon-Kenneth
Published: June 2020

Background: The measurement of lactate in emergency medical services has the potential for earlier detection of shock and can be performed with a point-of-care handheld device. Validation of a point-of-care handheld device is required for prehospital implementation. Aim: The primary aim was to validate the accuracy of Lactate Pro 2 in healthy volunteers and in haemodynamically compromised intensive care patients. The secondary aim was to evaluate which sample site, fingertip or earlobe, is most accurate compared to arterial lactate. Methods: Arterial, venous and capillary blood samples from fingertips and earlobes were collected from intensive care patients and healthy volunteers. Arterial and venous blood lactate samples were analysed on a stationary hospital blood gas analyser (ABL800 Flex) as the reference device and compared to the Lactate Pro 2. We used the Bland-Altman method to calculate the limits of agreement and used mixed effect models to compare instruments and sample sites. A total of 49 intensive care patients with elevated lactate and 11 healthy volunteers with elevated lactate were included. Results: There was no significant difference in measured lactate between Lactate Pro 2 and the reference method using arterial blood in either the healthy volunteers or the intensive care patients. Capillary lactate measurement in the fingertip and earlobe of intensive care patients was 47% (95% CI (29% to 68%), p<0.001) and 27% (95% CI (11% to 45%), p<0.001) higher, respectively, than the corresponding arterial blood lactate. In the healthy volunteers, we found that capillary blood lactate in the fingertip was 14% higher than arterial blood lactate (95% CI (4% to 24%), p= 0.003) and no significant difference between capillary blood lactate in the earlobe and arterial blood lactate.Conclusion: Our results showed that the handheld Lactate Pro 2 had good agreement with the reference method using arterial blood in both intensive care patients and healthy volunteers. However, we found that the agreement was poorer using venous blood in both groups. Furthermore, the earlobe may be a better sample site than the fingertip in intensive care patients.
Geospatial Approach For Assessment Of Vulnerability To Flood In Local Self Governments
Authors: S Deepak , Rajan Gopika , G Jairaj P
Published: June 2020

Recent years have shown a significant increase in the occurrence of flood globally, with impact on habitation and different sectors of the economy. This, in turn, necessitates the use of different flood mitigation strategies, wherein flood vulnerability assessment plays a significant role. The proposed work presents a methodology which combines vulnerability under physical-environmental and socio-economic domains to assess the overall flood vulnerability at the local self-government level. The methodology was illustrated to the case of Aluva municipality, located on the banks of River Periyar, in Kerala state, India. The spatial variation of hazard inducing factors and population statistics were analysed using Geographic Information System (GIS) tools. The machine learning algorithm, Random Forest, which uses hazard inducing factors as input was implemented for the evaluation of physical-environmental vulnerability. The social vulnerability of the region was analysed using GIS Multi-criteria decision analysis approach (MCDA), with criteria weights to incorporate the interests of different stakeholders. The critical combinations of the two domains of vulnerability in the assessment of the vulnerability to flood, to have efficient flood management in local self-government was demonstrated in this study and can be made use of for any flood event.
Effect of a telemedicine intervention for diabetes-related foot ulcers on health, well-being and quality of life: Secondary outcomes from a cluster randomized controlled trial (DiaFOTo)
Authors: Iversen Marjolein Memelink , Igland Jannicke , Smith-Strøm Hilde , Østbye Truls , Tell Grethe Seppola , Skeie Svein , Cooper John G. , Peyrot Mark , Graue Marit
Published: June 2020

BACKGROUND
Follow-up care provided via telemedicine (TM) is intended to be a more integrated care pathway to manage diabetes-related foot ulcers (DFU) than traditionally-delivered healthcare. However, knowledge of the effect of TM follow-up on PROMs including self-reported health, well-being and QOL in patients with DFUs is lacking and often neglected in RCT reports in general. Therefore, in this study of secondary outcomes from the DiaFOTo trial, the aim was to compare changes in self-reported health, well-being and QOL between patients with DFUs receiving telemedicine follow-up care in primary healthcare in collaboration with specialist healthcare, and patients receiving standard outpatient care.
METHODS
The current study reports secondary endpoints from a cluster randomized controlled trial whose primary endpoint was ulcer healing time. The trial included 182 adults with diabetes-related foot ulcers (94/88 in the telemedicine/standard care groups) in 42 municipalities/districts, recruited from three clinical sites in Western Norway. The intervention group received care in the community in collaboration with specialist healthcare using an asynchronous telemedicine intervention. The intervention included an interactive web-based ulcer record and a mobile phone enabling counseling and communication between the community nurses and specialist healthcare; the control group received standard outpatient care. In total 156 participants (78/78) reported on secondary endpoints: self-reported health, well-being and quality of life evaluated by generic and disease-specific patient-reported outcome measures (e.g. Euro-QOL, the Hospital Anxiety and Depression Scale (HADS), Problem Areas in Diabetes (PAID), Neuropathy and Foot Ulcer–Specific Quality of Life Instrument (NeuroQOL)). Linear mixed-effects regression was used to investigate possible differences in changes in the scores between the intervention and control group at the end of follow-up.
RESULTS
In intention to treat analyses, differences between treatment groups were small and non-significant for the health and well-being scale scores, as well as for diabetes-related distress and foot ulcer-specific quality of life.
CONCLUSIONS
There were no significant differences in changes in scores for the patient reported outcomes between the intervention and control group, indicating that the intervention did not affect the participants’ health, well-being and quality of life.
Cardiac MRI utilizing late gadolinium enhancement (LGE) and T1 mapping in the detection of radiation induced heart disease
Authors: Ricco Anthony , Slade Alexander , Canada Justin , Grizzard John , Dana Franklin , Gharai Leila Rezai , Neiderer Keith , Vera Armando , Abbate Antonio , Weiss Elisabeth
Published: June 2020

Background and Purpose: Radiotherapy has been associated with late dose-dependent cardiovascular toxicity. In this cross-sectional pilot study, radiation dose distributions were correlated with areas of localized and diffuse myocardial fibrosis as measured by novel cardiac MRI (CMR) sequences including late gadolinium enhancement (LGE) and T1 mapping with the goal to identify early markers of myocardial damage.Materials and Methods: Twenty-eight patients with chest tumors including lung, breast, esophagus, and lymphoma underwent CMR per study protocol on average 46.4 months (range 1.7-344.5) after radiotherapy. Patients without pretreatment cardiac history were included if the volume of heart receiving 5 Gy or more was at least 10% (V5Gy≥10%). The association of LGE with cardiac dosimetric factors, clinical factors (e.g., tumor type, smoking history, BMI), , and T1 values was analyzed. Results: Cardiac maximum (Dmax) and mean dose (Dmean) equivalent to doses delivered in 2 Gy fractions (EQD2) were on average 50.9 Gy (range 6.2-108.0) and 8.2 Gy (range 1.0-35.7), respectively, compared to 60.8 Gy (40.8-108.0) and 6.8 Gy (1.8-21.8) among the 9 patients with LGE. Doses were not different between patients with and without LGE (p=0.16 and 0.56, respectively). The average T1 value of the left ventricle myocardium was 1009 ms (range 933-1117). No significant correlation was seen for heart Dmax and Dmean and T1 values (p=0.14 and 0.58, respectively). In addition, no significant association between clinical factors and the development of LGE was identified.Conclusions: No relation between cardiac doses, the presence of LGE or T1 values was observed. Further study is needed to determine the benefit of CMR for detecting radiotherapy-related myocardial fibrosis.
Efficacy and Safety of Bevacizumab in Combination with Chemotherapy for Colorectal Cancer – A Real World Study in China
Authors: Shen Tao , Cheng Xian-Shuo , Chunyu Wei-Xun , Zhang Hong-Tao , Xia Cui-Feng , Pan Ding-Guo , Zhang Xuan , Tian Chang-Ping , Liang Rui , Yun-feng Li
Published: June 2020

Background

Large scale randomized trials have demonstrated that bevacizumab in addition to chemotherapy as first-line or second-line treatment has significant survival benefits. We aim to explore the clinical impact of bevacizumab in combination with chemotherapy in first-line or second-line in patients with colorectal cancer (CRC).
Methods

The medical records of patients with CRC who received bevacizumab at first or second-line of treatment were collected retrospectively. The primary outcome of the study was to evaluate the efficacy of bevacizumab in combination with chemotherapy by survival endpoints i.e. overall survival (OS) and progression-free survival (PFS) and the secondary outcome was to evaluate its safety by incidence of adverse events (AE).
Results

Fifty-one patients with CRC had met the selection criteria for treatment with bevacizumab to either cetuximab or FOLFOX or both. The median age was 54 years. During follow-up, ten patients had exhibited progression after treatment while 5 patients died. The median OS and PFS of the overall population were not reached. The Cox proportional regression analysis revealed no significant prognostic factors of OS and PFS for treatment with bevacizumab in various demographic subgroups. The 1-year PFS rates of all 51 patients was 76%. The 1-year and 3-year OS rates for all 51 patients were 95% and 88%, respectively. Toxicities were usually mild in nature, with nausea, vomiting, hand and foot syndrome, neutropenia, asthenia and palpitation being the commonly reported adverse events.
Conclusion

In this real-world setting, the efficacy and safety of bevacizumab in combination with chemotherapy is limited and further research is warranted as to whether bevacizumab with chemotherapy is an optimal treatment as first-line or second-line therapy in Chinese CRC patients.
Enhanced Growth Performance Of Microalgal Biomass For Lipid Production
Authors: Perez Ysa Francine , Maria Christine Ann Sta , Pineda Rence Marrion Mangulabnan , Aquino John Dave , Undan Jerwin
Published: June 2020

The supply of petroleum-based fuel decreases, and the need to produce viable renewable fuel increases. In the wake of the uprising global energy crisis, microalgae serve as a promising feedstock for oil production. The researcher gained interest due to its hitting-two birds-with-one-stone approach as a potential solution for the continuously depleting source of oil reservoir worldwide and to reduce carbon dioxide emission into the atmosphere using microalgae. The potential of the strains (Chlorella vulgaris, Monoraphidium sp., Scenedesmus obliquus, Desmodesmus denticulatus, and Chlorophyta sp.) in the production of lipid was assessed in this study. Furthermore, optimization of the growth conditions of each microalgae strain were identified to enhance biomass production and lipid accumulation. Two microalgae strains namely Monoraphidium sp. and Desmodesmus denticulatus exhibited higher lipid productivity compared to other microalgae strains on biomass and lipid content. The following optimized growth conditions that support algal growth are as follows: pH 5, 0.5 moles in salinity level, outside temperature, and sunlight. The production of lipids is dependent on the microalgae strain, including the optimum condition that supports its biomass production.
The influence of supplier-user relationships on user satisfaction in the healthcare sector: the provisioning case.
Authors: Vainieri Milena , Coletta Lucrezia , Seghieri Chiara
Published: June 2020

Background

Since 90 s customer orientation has become one of the main priorities in the public sector. While there are several studies dealing with final user satisfaction in the healthcare context, less attention has been given to inter-organizational relationships. This study aims at investigating the relationship between service quality, relationship quality and overall customer satisfaction in the case of a supplier-user provisioning service in the healthcare sector.
Methods

The analysis was based on a survey administered via CAWI (Computer Assisted Web Interviewing) to all professionals of the Tuscan health system. Moderation and mediation models were carried out to test the relationships between the three constructs, also differentiating among different customer typologies.
Results

Findings from the moderation model showed how different customers perceive relationship quality as differently influencing their overall satisfaction. This result was confirmed by the mediation models that showed how for one customer typology both relationship quality and service quality were relevant determinants of their satisfaction with supplier performance, even though relational aspects were more significant, compared to service aspects. Whereas, for the second customer typology overall satisfaction was influenced by characteristics concerning relationship quality only, suggesting that service quality dimension was not relevant in determining overall satisfaction.
Conclusions

In the healthcare provisioning case analyzed, different customers’ typologies have different expectations and weigh differently service related and relationship related aspects. Supplier should use different levers in order to enhance customers’ perceptions about the overall performance.
Development of An Immunogenomic Landscape For The Competing Endogenous RNAs Network of Peri-Implantitis
Authors: Li Yang , Zheng Ji-Na , Gong Chan-Juan , Lan Keng-Fu , Ding XiaoJun
Published: June 2020

Background: Peri-implantitis is an inflammation that occurs around the implant, resulting in varying degrees of inflammatory damage to the soft and hard tissues. The characteristic criterion is the loss of the supporting bone in an inflammatory environment. However, the specific mechanisms and biomarkers involved in peri-implantitis remain to be further studied. Recently, competing endogenous RNAs (ceRNA) and immune microenvironment have been found to play a more important role in the inflammatory process. In our study, we analyzed the expression of immune related microRNAs (miRNAs), long noncoding RNAs (lncRNAs) and message RNAs (mRNAs) in peri-implantitis by analyzing GSE33774 and GSE57631.Methods: In this study, we explored the expression profile data of immune-related lncRNAs, miRNAs and mRNAs, and constructed immune-related ceRNA network involved in the pathogenesis of peri-implantitis. In addition, the CIBERSORT was used to evaluate the content of immune cells in normal tissues and peri-implantitis to detect the immune microenvironment of peri-implantitis.Results: In the analysis, the corresponding lncRNAs, 14 DElncRNAs, 16 DEmiRNAs, and 18 DEmRNAs were used to establish an immune related ceRNA network constructed and the immune infiltration patterns associated with peri-implantitis was discovered. Through the mutual verification of the two datasets, we found that GSK3B and miR-1297 may have important significance in the immune microenvironment and pathogenesis of peri-implantitis and GSK3B was closely related to four types of immune cells, which needs to be further proved by later experiments. Conclusions: Through immune-related ceRNA network, IRGs and immune cell infiltration can further comprehensively understand the pathogenesis of peri-implantitis, which built up an immunogenomic landscape with clinical significance for peri-implantitis.One-sentences summary: GSK3B and miR-1297 may have important significance in the immune microenvironment and pathogenesis of peri-implantitis.
Reactive Oxygen Species Modulator-1 (ROMO-1) Polymorphism Rs6060566 and The Risk of Myocardial Infarction in Slovenian Subjects With Type 2 Diabetes Mellitus
Authors: Tibaut Miha , Ramuš Sara Mankoč , Petrovič Daniel
Published: June 2020

Background
We aimed to examine the role of the rs6060566 polymorphism of the reactive oxygen species modulator-1 (ROMO-1) gene in the development of myocardial infarction (MI) in Caucasians with type 2 diabetes mellitus (T2DM).
Methods
A total of 1072 subjects with T2DM were enrolled in cross-sectional case-control study: 335 subjects with MI and 737 subjects without clinical signs of coronary artery disease (CAD). Genetic analysis of the rs6060566 polymorphism was performed in all subjects. To assess the degree of coronary artery obstruction, a subpopulation of 128 subjects with T2DM underwent coronary computed tomography (CT) angiography. Next, endarterectomy samples were obtained during myocardial revascularization from diffusely diseased coronary arteries in 40 cases, which were analysed for ROMO-1 expression according to their genotype.
Results
There were no statistically significant associations between different genotypes or alleles of the rs6060566 polymorphism and MI in subjects with T2DM. The carriers of the C allele of the ROMO-1 rs6060566 had a threefold increased likelihood of having coronary artery stenosis (AOR = 3.27, 95% CI 1.16–9.20). Furthermore, the carriers of the C allele showed higher number of positive cells for ROMO-1 expression in endarterectomy samples of coronary arteries.
Conclusions
In accordance to our study, the rs6060566 polymorphism of the ROMO-1 gene is not the risk factor for MI in Caucasians with T2DM. However, we found that subjects carrying the C allele were at a 3.27-fold increased risk of developing severe CAD compared with those who had nonobstructive CAD. Moreover, The C allele carriers showed statistically higher number of cells positive for ROMO-1 compared with T allele carriers in coronary endarterectomy samples.
Healthcare professionals´ experiences of assessing, treating and preventing constipation among older patients during hospitalization: An interview study
Authors: Lundberg Veronica , RN Anne-Marie Boström , Gottberg Kristina , Konradsen Hanne
Published: June 2020

Background
Constipation is a common and troublesome condition among older patients and can result in a variety of negative health consequences. It is often undiagnosed or undertreated. Healthcare professionals have a responsibility to understand and address patients’ overall healthcare needs so exploring their experiences is, therefore, highly relevant. The purpose of the study was to explore healthcare professionals’ experiences of assessing, treating and preventing constipation among older patients.
Methods
A qualitative design with an exploratory approach was used. The participants were purposively sampled from three wards in a geriatric department in a medium-sized hospital in Sweden. Data were collected through focus group interviews and individual interviews and analyzed using content analysis.
Results
Three categories were generated: depending on resources and uncertainties, using different strategies, and approaching the patients’ needs. In the care of older patients at risk of or with constipation, decisions were made based on personal knowledge, personal experience and clinical reasoning. A person-centered approach was highlighted but was not always possible to incorporate.
Conclusions
Different strategies for preventing and treating constipation were believed to be important, as was person-centered care, but were found to be difficult to perform. Healthcare professionals need adequate resources. Evidence-based clinical guidelines might help the delivery of high-quality care. Constipation needs to be given more focus in hospitals in order to potentially improve the care and patient outcomes for older people.
Association Between Single-Nucleotide Polymorphisms in Breast Cancer Susceptibility Genes and Clinicopathological Characteristics
Authors: Zhang Kejing , Tang Lili , Wang Shouman , Yang Yuan , Wang Hao , Zhou Zhiyang , Pang Jian , Chen Feiyu
Published: June 2020

Objective

The purpose of the present study was to evaluate the associations between seven tagging single nucleotide polymorphisms (tSNPs) and risk of breast cancer assessed by tumor pathological characteristics and body mass index (BMI).
Methods

Seven tSNPs of four breast cancer susceptibility genes were analyzed in 734 Chinese women with breast cancer and 672 age-matched healthy controls, then the association with clinicopathological characteristics, BMI, molecular subtype, TNM staging and lymph node status, was determined.
Results

Two tSNPs, rs12951053 located in TP53 and rs16945628 in BRIP1, displayed increased risk of breast cancer in the BMI ≧ 25 kg/m2 group (OR = 1.50, 95% CI: 1.02–2.21, P = 0.041 and OR = 1.92, 95% CI: 1.13–3.26, P = 0.015, respectively). The other five tSNPs (rs1805812, rs2735385 and rs6999227 in NBS1, rs7220719 in BRIP1 and rs2299941 in PTEN) displayed a decreased risk of breast cancer in the 18.5 ≤ BMI < 25 kg/m2 group. Two tSNPs, rs12951053 in TP53 and rs7220719 in BRIP1 exhibited an increased risk of triple-negative breast cancer(TNBC) (OR = 1.50, 95% CI: 1.05–2.15, P = 0.026 and OR = 2.13, 95% CI: 1.05–4.29, P = 0.032, respectively), and the three tSNPs in NBS1 (rs1805812, rs2735385 and rs6999227) all displayed negative association with both luminal B breast cancer and TNBC. The tSNP rs2299941 in PTEN also exhibited a negative association with each breast cancer molecular subtype, except TNBC. The majority of tSNPs displayed a negative association with stage II or III breast cancer. A number of tSNPs showed a negative association with breast cancer that was lymph node negative or with 1–3 positive nodes. Only one tSNP, rs12951053 in TP53 displayed a positive association with lymph node negative breast cancer (OR = 1.43, 95% CI: 1.08–1.91, P = 0.013).
Conclusions

The majority of tSNPs displayed a negative association with breast cancer and only a few tSNPs (rs12951053 in TP53, rs16945628 and rs7220719 in BRIP1) showed an increased risk of breast cancer as defined by clinicopathological characteristics.
Opportunities and challenges to Integrating mental health into HIV programs in a Low- and Middle-Income Country: Insights from the Nigeria Implementation Science Alliance
Authors: Ezeanolue Echezona E , Iheanacho Theddeus , Adedeji Isaac , Itanyi Ijeoma , Olakunde Babayemi , Patel Dina , Dakum Patrick , Okonkwo Propser , Akinmurele Timothy , Obiefune Michael , Khamofu Hadiza , Oyeledun Bolanle , Aina Muyiwa , Eyo Andy , Oleribe Obinna , Oko John , Olutola Ayodotun , Gobir Ibrahim , Aliyu Muktar H , Aliyu Gambo , Woelk Godfrey , Aarons Gregory , Siberry George , Sturke Rachel , ASSISTANT NISA
Published: June 2020

Background: In Nigeria, there is an estimated 1.9 million people living with HIV (PLHIV), 53% of whom utilize HIV care and services. With decreasing HIV-related deaths and increasing new infections, HIV with its associated comorbidities continue to be a key public health challenge in Nigeria. Untreated, comorbid mental disorders are a critical but potentially modifiable determinant of optimal HIV treatment outcomes. This study aimed to identify the challenges and opportunities related to integrating mental health care into existing HIV programs in Nigeria.Method: Attendees at the Nigeria Implementation Science Alliance (NISA)’s 2019 conference participated in nominal group technique (NGT) exercise informed by the “Exploration, Preparation, Implementation, and Sustainment (EPIS)” framework. The NGT process was conducted among the nominal groups in two major sessions of 30-minutes phases followed by a 30-minute plenary session. Data analysis proceeded in four steps: transcription, collation, theming and content analysis.Results: The two major theoretical themes from the study were – opportunities and challenges of integrating mental health treatment into HIV services. Three sub-themes emerged on opportunities: building on health care facilities for HIV services (screening, counseling, task-sharing monitoring and evaluation frameworks) , utilizing existing human resources or workforce in HIV programs (in-service training and including mental health in education curriculum) and the role of social and cultural structures (leveraging existing community, traditional and faith-based infrastructures). Four sub-themes emerged for challenges: double burden of stigma and the problems of early detection (HIV and mental health stigma, lack of awareness) , existing policy gaps and structural challenges (fragmented health system) , limited human resources for mental health care in Nigeria (knowledge gap and burnout) and dearth of data/evidence for planning and action (research gaps) .Conclusions: Potential for integrating treatments for mental disorders into HIV services exist in Nigeria. These include opportunities for clinicians’ training and capacity building as well as community partnerships. Multiple barriers and challenges such as stigma, policy and research gaps would need to be addressed to leverage these opportunities. Our findings serve as a useful guide for government agencies, policy makers and research organizations to address co-morbid mental disorders among PLHIV in Nigeria.
Conprehensive Analysis of circRNA-microRNA-mRNA Network Revealed Novel Regulatory Mechanism in Trichosposon Asahii Infection
Authors: Zhang Ming-Wang , Zhu Zhi-Hong , Xia Zhi-Kuan , Yang Xin , Luo Wan-Ting , Ao Jun-Hong , Yang Rong-Ya
Published: June 2020

Background: Trichosporon asahii (T. asahii) invasive infection frequently occurs in immunodeficient hosts with high mortality, but the pathogenesis of T. asahii infection remains elusive. Circular RNAs (circRNAs) are a type of endogenous noncoding RNAs that participant various disease processes. However, the mechanism of circRNAs in T. asahii infection are still completely unknown.Methods: RNA sequencing (RNA-seq) was performed to analyse the expression profiles of circRNA, microRNA (miRNA), and mRNA in THP-1 cells infected with T. asahii or uninfected samples. Part of the RNA-seq results were verified by RT-qPCR. Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were used to analyse the differentially expressed (DE) mRNA. The circRNA-miRNA-mRNA network was constructed and verified with dual-luciferase reporter assay and overexpression experiment.Results: A total of 46 circRNAs , 412 mRNAs and 47 miRNAs were DE after T. asahii infection at 12 h. GO and KEGG analysis showed that the DE mRNAs were primary linked to the leukocyte migration involved in inflammatory response, Toll-like receptor signaling pathway, and TNF signaling pathway. A competing endogenous RNA (ceRNA) network was constructed with five DE circRNAs, five DE miRNAs and 42 DE mRNAs. Among them, we verified that hsa_circ_0065336 indirectly regulate PTPN11 expression by sponging miR-505-3p.Conclusions: These data revealed a comprehensive circRNA-associated ceRNA network during T. asahii infection, thus providing new insights to clarify the pathogenesis between T. asahii-host interation.
Skewed expression profile of receptors for BAFF on peripheral blood B lymphocytes in Graves’ Disease
Authors: Wang Xin , Huang Jinhui , Zhang Aixia , Fang Chen , Ma Qi , Jiang Penjun
Published: June 2020

Background
Previous studies have demonstrated altered serum B lymphocyte activating factor (BAFF) level and expression of BAFF and BAFF receptor (BAFF-R) in thyroid infiltrating lymphocytes in Graves’ disease (GD) patients. The aim of the present study was to investigate expression of receptors for BAFF on the peripheral blood B lymphocytes in addition to serum BAFF concentrations.
Methods
Fifty-two GD patients and twenty-three healthy controls (HC) were recruited in this study. Serum BAFF concentrations were measure by ELISA. Expression of receptors for BAFF on peripheral blood B lymphocytes, including BAFF-R and transmembrane activator and calcium-modulating and cyclophilin ligand interactor (TACI), was analyzed by flow cytometry. Serum BAFF levels, expression of BAFF-R and TACI on peripheral blood B lymphocytes were compared between GD and HC groups. Correlations between serum BAFF concentrations and thyroid function and thyrotropin receptor autoantibody (TRAb) titers were analyzed in GD patients. In 10 patients with Graves’ orbitopathy (GO) receiving steroids therapy, effects of steroids on serum BAFF levels and expression of BAFF-R and TACI were observed.
Results
Serum BAFF levels were significantly higher in GD patients (1.18 ± 0.33 ng/ml) than those in HC (0.93 ± 0.24 ng/ml, P = 0.0011). In GD patients, serum BAFF levels correlated positively with free thyroxine concentrations (Spearman r = 0.2460, P = 0.0394), but not TRAb titers (P = 0.4734). BAFF-R expression on peripheral B lymphocytes were elevated in GD (mean MFI: 4.52 ± 2.06 in GD vs 3.00 ± 0.87 in HC, P < 0.0001), while TACI expression on peripheral B lymphocytes were decreased in GD (mean MFI: 7.96 ± 4.06 in GD vs 9.10 ± 3.37 in HC, P = 0.0331). Steroids significantly suppressed serum BAFF concentrations ( from 1.18 ± 0.27 ng/ml to 0.97 ± 0.10 ng/ml, P = 0.0364) and BAFF-R expression on peripheral blood B lymphocytes in GO patients (mean MFI from 6.26 ± 4.91 to 4.05 ± 1.58, P = 0.0083). Change of TACI expression on B lymphocytes was not statistically significant after steroids therapy.
Conclusions
Skewed expression profile of receptors for BAFF on B lymphocytes may mediate the autoimmunity in GD. Restoring the normal expression profile of receptors for BAFF could be a new strategy for treating and cueing GD.