bluuebunny/crossref_metadata_2025 huggingface dataset:
Dynamic changes of neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio predicts breast cancer prognosis
Authors: Kim Ju-Yeon , Jung Eun Jung , Kim Jae-Myung , Lee Han Shin , Kwag Seung-Jin , Park Ji-Ho , Park Taejin , Jeong Sang-Ho , Jeong Chi-Young , Ju Young-Tae
Published: December 2020

Background: We aimed to identify whether neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) are more useful predictors after initial intention to treat than at the time of diagnosis.Methods: We collected the medical data of 533 patients. The results of the peripheral blood sampling before the primary treatments were labeled as initial cohort, and those obtained between 24 and 36 months after initial treatment were defined as the 2nd cohort. Delayed metastasis has been defined as distant metastasis 2 years after treatment, and survival outcome was estimated and compared across groups. Results: Median follow-up duration was 74 months (24–162 months), and 53 patients experienced delayed metastasis. In univariate analysis, metastasis-free survival, patient age at diagnosis, tumor size, axillary lymph node metastasis, HER-2 status, initial NLR and PLR, and 2nd NLR and PLR were found to be significantly associated with delayed metastasis. However, in multivariate analysis, only the 2nd NLR and PLR were found to be significantly associated with delayed metastasis, excluding initial NLR and PLR. Metastasis-free survival was analyzed through the pattern changes of NLR or PLR. The results revealed that patients with continued low NLR and PLR values at pre- and post-treatment (low initial values and 2nd values) showed a significantly better prognosis than those with a change in value or continued high NLR and PLR. Conclusions: We identified that patients with persistent high NLR and PLR after initial treatment have significant worse prognosis in terms of late metastasis. Therefore, these results suggest that NLR and PLR are more useful in predicting prognosis post-treatment.
Prediction of mechanical ventilation greater than 24 hours in critically ill obstetric patients: Ten years of data from a tertiary teaching hospital in mainland China
Authors: Zhao Huiying , Wang Guangjie , Lyu Jie , Zhang Xiaohong , An Youzhong
Published: December 2020

Background: Maternal admission to the intensive care unit (ICU) during pregnancy or in the postpartum period is a marker of severe acute maternal morbidity. Mechanical ventilation is an important and basic method of maintaining life support in the ICU, but prolonged mechanical ventilation (PMV) is associated with a prolonged length of hospital stay and other adverse outcomes. Therefore, we conducted this retrospective study to describe morbidity and further try to identify the risk factors for PMV in critically ill obstetric women.Methods: The clinical data were obtained from a single-centre retrospective comparative study of 143 critically ill obstetric patients at a tertiary teaching hospital in mainland China between January 1, 2009, and December 31, 2019. PMV was defined as a mechanical ventilation length of more than 24 hours. Clinical and obstetric parameters were collected to analyse the risk factors for PMV. Patients were separated into groups with and without PMV. Potential risk factors were identified by univariate testing. Multivariate logistic regression was used to evaluate independent predictors of PMV.Results: Out of 29,236 hospital deliveries, 265 critically ill obstetric patients entered the ICU. One hundred forty-five (54.7%) of them were treated with mechanical ventilation. Two were excluded because of death within 24 hours. Sixty-five critically ill obstetric patients (45.5%) underwent PMV. The independent risk factors for PMV included estimated blood loss (odds ratio (OR) =1.296, P=0.029), acute kidney injury (AKI) (OR=4.305, P=0.013), myocardial injury (OR=4.586, P=0.012), and PaO2/FiO2 (OR=0.989, P<0.001). The area under the receiver operating characteristic (ROC) curve based on the predicted probability of the logistic regression was 0.934.Conclusions: Estimated blood loss, AKI, myocardial injury, and PaO2/FiO2 were independent risk factors for PMV in critically ill obstetric patients.
EML4-ALK induces cellular senescence in mortal normal human cells and promotes anchorage-independent growth in hTERT-transduced normal human cells
Authors: Miyanaga Akihiko , Matsumoto Masaru , Beck Jessica A. , Horikawa Izumi , Oike Takahiro , Okayama Hirokazu , Tanaka Hiromi , Burkett Sandra S. , Robles Ana I. , Khan Mohammed , Lissa Delphine , Seike Masahiro , Gemma Akihiko , Mano Hiroyuki , Harris Curtis C.
Published: December 2020

Background: Chromosomal inversions involving anaplastic lymphoma kinase (ALK) and echinoderm microtubule associated protein like 4 (EML4) generate a fusion protein EML4-ALK in non-small cell lung cancer (NSCLC). The understanding of EML4-ALK function can be improved by a functional study using normal human cells.Methods: Here we for the first time conduct such study to examine the effects of EML4-ALK on cell proliferation, cellular senescence, DNA damage, gene expression profiles and transformed phenotypes.Results: The lentiviral expression of EML4-ALK in mortal, normal human fibroblasts caused, through its constitutive ALK kinase activity, an early induction of cellular senescence with accumulated DNA damage, upregulation of p16INK4A and p21WAF1, and senescence-associated b-galactosidase (SA-β-gal) activity. In contrast, when EML4-ALK was expressed in normal human fibroblasts transduced with telomerase reverse transcriptase (hTERT), which is activated in the vast majority of NSCLC, the cells showed accelerated proliferation and acquired anchorage-independent growth ability in soft-agar medium, without accumulated DNA damage, chromosome aberration, nor p53 mutation. EML4-ALK induced the phosphorylation of STAT3 in both mortal and hTERT-transduced cells, but RNA sequencing analysis suggested that the different signaling pathways contributed to the different phenotypic outcomes in these cells. While EML4-ALK also induced anchorage-independent growth in hTERT-immortalized human bronchial epithelial cells in vitro, the expression of EML4-ALK alone did not cause detectable in vivo tumorigenicity in immunodeficient mice.Conclusions: Our data indicate that the expression of hTERT is critical for EML4-ALK to manifest its in vitro transforming activity in human cells. This study provides the isogenic pairs of human cells with and without EML4-ALK expression.
A phase II study of first-line afatinib for patients aged ≥75 years with EGFR mutation-positive advanced non-small cell lung cancer: North East Japan Study Group Trial NEJ027
Authors: Minegishi Yuji , Yamaguchi Ou , Sugawara Shunichi , Kuyama Shoichi , Watanabe Satoshi , Usui Kazuhiro , Mori Masahide , Hataji Osamu , Nukiwa Toshihiro , Morita Satoshi , Kobayashi Kunihiko , Gemma Akihiko
Published: December 2020

Background: Lung cancer is most common among older individuals. However, polypharmacy and comorbidities, which are also more common in older individuals, can limit treatment options. Previous studies suggest that afatinib can be used safely and effectively in elderly patients. This study investigated the anti-tumour activity and safety profile of first-line afatinib in previously-untreated elderly Japanese patients with EGFR mutation-positive non-small cell lung cancer (NSCLC)Methods: This was a single-arm, open-label, phase II study, performed in multiple centres in Japan. Previously untreated patients, aged ≥75 years, with EGFR mutation-positive (Del19 or L858R) advanced NSCLC were treated with afatinib 40 mg until disease progression or unacceptable toxicity. Adverse events (AEs) were managed with protocol-defined dose adjustments. The primary endpoint was objective response rate (ORR) by central review. Results: In total, 38 patients received at least one dose of afatinib, and 37 were evaluable for response. Median age was 77.5 years (range 75–91), all patients had an Eastern Cooperative Oncology Group performance status of 0 or 1, and 60.5% had Del19-positive disease. Median follow-up was 838 days. ORR was 75.7% (2 complete responses and 26 partial responses). Median progression-free survival was 14.2 months (95% confidence interval [CI], 9.5–19.0). Median overall survival (OS) was 35.2 months (95% CI, 35.2–not reached); the 2-year OS rate was 78.3%. The most common grade III/IV treatment-related AEs (TRAEs) were diarrhoea (28.9%), paronychia (23.7%), and rash/acne (15.8%). Dose reductions due to TRAEs were reported in 78.9% of patients, and 8 (21.1%) patients discontinued afatinib due to TRAEs. No treatment-related deaths were reported.Conclusion: Although dose adjustments were relatively common in this small group of Japanese patients aged ≥75 years with EGFR mutation-positive NSCLC, discontinuation occurred much less frequently, and most patients were able to stay on treatment for well over a year. Further, afatinib was associated with high response rates and prolonged PFS and OS.Trial Registration: The trial is registered with Japan Registry of Clinical Trials (JRCT) as trial number 031180136 (date of initial registration: 19 February 2019), and the University Hospital Network (UMIN) as trial number 000017877 (date of initial registration: 11 June 2015).
A qualitative meta-synthesis of facilitators and barriers to tuberculosis diagnosis and treatment in Nigeria
Authors: Oga-Omenka Charity , Wakdet Lawrence , Menzies Dick , Zarowsky Christina
Published: December 2020

Background Despite progress in tuberculosis (TB) control globally, TB continues to be a leading cause of death from infectious diseases, claiming 1.2 million lives in 2018; 214,000 of these deaths were due to drug resistant strains. Of the estimated 10 million cases globally in 2018, 24% were in Africa, with Nigeria and South Africa making up most of these numbers.Nigeria ranks 6th in the world for TB burden, with an estimated 4.3% multi-drug resistance in new cases. However, the country had one of the lowest case detection rates, estimated at 24% of incident cases in 2018 - well below the WHO STOP TB target of 84%. This rate highlights the need to understand contextual issues influencing tuberculosis management in Nigeria. Our synthesis was aimed at synthesizing qualitative evidence on factors influencing TB care in Nigeria. Methods A three-stage thematic meta-synthesis of qualitative studies was used to identify barriers and facilitators to tuberculosis case finding and treatment in Nigeria. A search of eleven databases was conducted. The date of publication was limited to 2006 to June 2020. We analyzed articles using a three-stage process, resulting in coding, descriptive subthemes and analytical themes.Results Our final synthesis of 10 articles resulted in several categories including community and family involvement, education and knowledge, attitudes and stigma, alternative care options, health system factors (including coverage and human resource), gender, and direct and indirect cost of care. These were grouped into three major themes: individual factors; interpersonal influences; and health system factors.Conclusion Case finding and treatment for TB in Nigeria currently depends more on individual patients presenting voluntarily to the hospital for care, necessitating an understanding of patient behaviors towards TB diagnosis and treatment. Our synthesis has identified several related factors that shape patients’ behavior towards TB management at individual, community and health system levels that can inform future interventions.
‘Key stakeholder perspectives on the development and real-world implementation of a home-based physical activity program for mothers at risk of postnatal depression: A qualitative study’
Authors: Teychenne Megan , Apostolopoulos Maria , Ball Kylie , Olander Ellinor K , Opie Rachelle S , Rosenbaum Simon , Laws Rachel
Published: December 2020

Background Physical activity (PA) is a modifiable risk factor for postnatal depression (PND) and programs are needed to enhance PA amongst women at risk of PND. Key stakeholder involvement in informing development and implementation of such programs is vital. However, little research demonstrates key stakeholder insights to inform the design and delivery of PA programs for improving PND. The aim of this study was to explore key stakeholder perspectives on the design and delivery of a home-based PA program for mothers with PND symptoms to inform future real-world implementation and scale-up.Methods A descriptive qualitative study was undertaken whereby semi-structured interviews were conducted with representatives from various key stakeholder organisations involved in postnatal PA and/or mental health, public health and policy in Australia (n=11). Interviews were conducted between September to November 2019 and explored stakeholder perceptions on the design and delivery of a home-based PA program for mothers with PND symptoms. The interview schedule was informed by both the Consolidated Framework for Implementation Research (CFIR) and the PRACTical planning for Implementation and Scale-up (PRACTIS) guide. Data were analysed thematically using both deductive and inductive coding. Results The relative priority of PND and PA was high for most organisations involved, although none implemented PA programs supporting women at risk of PND. Most stakeholders perceived the program as appealing due to addressing barriers to postnatal PA, although identified some feasibility issues regarding funding and delivery mechanisms. Suggestions for program adaptations included an equity focus (e.g. providing socioeconomically disadvantaged women with a greater program dose; translating web-app based content into various languages). Planned components of the program were suggested to align (i.e. relative advantage) with existing initiatives (e.g. equipment hire for nurseries scheme) and screening systems for PND (timing of referral). Perceived barriers to scale-up included logistics/cost of equipment, organisational capacity demands and safety risks/liability. Perceived enablers to scale-up included linking the program with ‘adjunct’ programs and services. Conclusions While the program was appealing and most organisations could see a role in endorsing and/or referring to the program, funding and delivery mechanisms still need to be identified.
Early clearance of serum HE4 and CA125 in predicting platinum sensitivity and prognosis in epithelial ovarian cancer
Authors: Rong Yan , Li Li
Published: December 2020

Objectives: To assess the clinical value of early clearance of HE4 and CA125 for platinum sensitivity and prognosis in patients with ovarian cancer.Method: HE4 and CA125 value including clinical data of 89 patients with ovarian cancer were collected. The clearance of HE4 and CA125 were assessed base on the platinum sensitivity, two-year PFS, PFS and OS.Results: 16 patients were classified as platinum resistant and 73 as platinum sensitive according to the response to platinum-base chemotherapy. When HE4 clearance after 3rd cycle chemotherapy or CA125 clearance after 1st cycle chemotherapy, it gave the highest AUC of 0.788, with 100% of sensitivity and 57.5% of specificity respectively between platinum resistant and platinum sensitive group. In addition, 59 patients were classified as two-year PFS group and 30 as not achieved two-year PFS group according to obtaining two-year PFS or not. It gave the highest AUC of 0.730, with 83.3% of sensitivity and 62.7% of specificity respectively when HE4 clearance after 3rd cycle chemotherapy or CA125 clearance after 1st cycle. The prolonged PFS and OS were significantly associated by the clearance of HE4 after 3rd cycle chemotherapy (p<0.0001, p<0.0001) as well as CA125 after 1st cycle chemotherapy (p<0.0001, p<0.0001).Conclusions: Our data suggested that the early clearance of HE4 and CA125 could predict platinum response and prognosis in patients with ovarian cancer. Monitoring the HE4 and CA125 during first-line chemotherapy might be helpful in predicting platinum sensitivity and risk to progress and relapse.
The fluid management and hemodynamic characteristics of PiCCO employed on young children with severe Hand, Foot, and Mouth Disease—a retrospective study
Authors: Wang Fengyun , Qiang Xinhua , Jiang Suhua , Shao Jingsong , Fang Bin , Zhou Lixin
Published: December 2020

Background Hand, foot, and mouth disease (HFMD) is an acute infectious disease caused by human enterovirus 71 (EV71), coxsackievirus, or echovirus, which are particularly common in preschool children. Severe HFMD is prone to cause pulmonary edema, and successively progresses to respiratory and circulatory failure; thus hemodynamic monitoring and fluid management are important in the treatment process. Methods We reviewed young patients with severe HFMD, caused by EV71, and who had been successfully treated in our department. A total of 20 patients met the inclusion criteria. Eight cases were monitored by the pulse indicator continuous cardiac output (PiCCO) technique, and fluid management was administered according to its parameters. With regard to the treatment with PiCCO monitoring, patients were divided into two groups: the PiCCO group (8 patients) and the control group (12 patients). The groups were then compared comprehensively to evaluate whether PiCCO monitoring could improve the clinical outcomes. Results After analysis, the findings were that although PiCCO failed to shorten the length of ICU stay, reduce the days of vasoactive drug usage, or reduce the number of cases which needed mechanical ventilation, it did reduce the incidence of fluid overload (p=0.085) and shortened the days of mechanical ventilation (p=0.028). After effective treatment, PiCCO monitoring showed that the cardiac index (CI) increased gradually(p<0.0001), whereas the pulse (P, p<0.0001), the extra vascular lung water index (EVLWI, p<0.0001), the global end diastolic volume index (GEDVI, p=0.0043), and the systemic vascular resistance index (SVRI, p<0.0001) all decreased gradually. Conclusion Our study discovered that PiCCO hemodynamic monitoring in young children with severe HFMD has potential clinical benefits, such as reducing fluid overload and duration of mechanical ventilation. However, whether it can ameliorate the severity of the disease, reduce mortality, or prevent multiple organ dysfunction remain to be further investigated.
Protein signature of human skin fibroblasts allows the study of the molecular etiology of rare neurological diseases
Authors: Hentschel Andreas , Czech Artur , Münchberg Ute , Freier Erik , Schara-Schmidt Ulrike , Sickmann Albert , Reimann Jens , Roos Andreas
Published: December 2020

Background: The elucidation of pathomechanisms leading to the manifestation of rare (genetically caused) neurological diseases including neuromuscular diseases (NMD) represents an important step toward the understanding of the genesis of the respective disease and might help to define starting points for (new) therapeutic intervention concepts. However, these “discovery studies” are often limited by the availability of human biomaterial. Moreover, given that results of next-generation-sequencing approaches frequently result in the identification of ambiguous variants, testing of their pathogenicity is crucial but also depending on patient-derived material. Methods: Human skin fibroblasts were used to generate a spectral library using pH8-fractionation of followed by nano LC-MS/MS. Afterwards, Allgrove-patient derived fibroblasts were subjected to a data independent acquisition approach (DIA). In addition, proteomic signature of an enriched nuclear protein fraction was studied. Proteomic findings were confirmed by immunofluorescence in a muscle biopsy derived from the same patient and cellular lipid homeostasis in the cause of Allgrove syndrome was analysed by fluorescence (BODIPY-staining) and coherent anti-Stokes Raman scattering (CARS) microscopy. Results: To systematically address the question if human skin fibroblasts might serve as valuable biomaterial for (molecular) studies of NMD, we generated a protein library cataloguing 8280 proteins including a variety of such linked to genetic forms of motoneuron diseases, congenital myasthenic syndromes, neuropathies and muscle disorders. In silico-based pathway analyses revealed expression of a diversity of proteins involved in muscle contraction and such decisive for neuronal function and maintenance suggesting the suitability of human skin fibroblasts to study the etiology of NMD. Based on these findings, next we aimed to further demonstrate the suitability of this in vitro model to study NMD by a use case: the proteomic signature of fibroblasts derived from an Allgrove-patient was studied. Dysregulation of paradigmatic proteins could be confirmed in muscle biopsy of the patient and protein-functions could be linked to neurological symptoms known for this disease. Moreover, proteomic investigation of nuclear protein composition allowed the identification of protein-dysregulations according with structural perturbations observed in the muscle biopsy. BODIPY-staining on fibroblasts and CARS microscopy on muscle biopsy suggest altered lipid storage as part of the underlying disease etiology. Conclusions: our combined data reveal that human fibroblasts may serve as an in vitro system to study the molecular etiology of rare neurological diseases exemplified on Allgrove syndrome in an unbiased fashion.
Long-term target tracking combined with re-detection
Authors: Wang Juanjuan , Yang HaoRan , Xu Ning , Wu Chengqin , Zhao ZengShun , Zhang Jixiang , Wu Dapeng Oliver
Published: December 2020

The long-term visual tracking undergoes more challenges and is closer to realistic applications than short-term tracking. However, the performances of most existing methods have been limited in the long-term tracking tasks. In this work, we present a reliable yet simple long-term tracking method, which extends the state-of-the-art Learning Adaptive Discriminative Correlation Filters (LADCF) tracking algorithm with a re-detection component based on the SVM model. The LADCF tracking algorithm localizes the target in each frame and the re-detector is able to efficiently re-detect the target in the whole image when the tracking fails. We further introduce a robust confidence degree evaluation criterion that combines the maximum response criterion and the average peak-to correlation energy (APCE) to judge the confidence level of the predicted target. When the confidence degree is generally high, the SVM is updated accordingly. If the confidence drops sharply, the SVM re-detects the target. We perform extensive experiments on the OTB-2015 and UAV123 datasets. The experimental results demonstrate the effectiveness of our algorithm in long-term tracking.
Using exosomal miRNAs extracted from porcine follicular fluid to investigate their role in oocyte development
Authors: Hu Junhe , Dong Jinyi , Zeng Zhi , Wu Juan , Tan Xiansheng , Tang Tao , Yan Jiao , Jin Chenzhong
Published: December 2020

Background: Follicular development is crucial to normal oocyte maturation, with follicular size closely related to oocyte maturation. To better understand the molecular mechanisms behind porcine oocyte maturation, we obtained exosomal miRNA from porcine follicular fluid (PFF). These miRNA samples were then sequenced and analyzed regarding their different follicular sizes, as described in the methods section. Results：First, these results showed that this process successfully isolated PFF exosomes. Nearly all valid reads from the PFF exosomal sequencing data were successfully mapped to the porcine genome database. Second, we used hierarchical clustering methods to determine that significantly expressed miRNAs were clustered into A, B, C, and D groups in our heatmap according to different follicle sizes. These results allowed for the targeting of potential mRNAs genes related to porcine oocyte development. Third, we chose ten, significantly expressed miRNAs and predicted their target genes for further GO analysis. These results showed that the expression levels of neurotransmitter secretion genes were greatly changed, as were many target genes involved in the regulation of FSH secretion. Notably, these are genes that are very closely related to oocyte maturation in growing follicles. We then used pathway analysis for these targeted genes based on the originally selected ten miRNAs. Results indicated that the pathways were mainly related to the biosynthesis of TGF-beta and its signaling pathway, which are very closely related to reproductive system functions.Conclusions：Finally, these exosomal miRNAs obtained from PFF may provide a valuable addition to our understanding of the mechanism of porcine oocyte maturation. It is also likely that these exosomal miRNAs could function as molecular biomarkers to choose high-quality oocytes and allow for in vitro porcine embryo production.
Effect of a 980-nm diode laser on post-operative pain after endodontic treatment in teeth with apical periodontitis: A randomized clinical trial
Authors: Kaplan Tuna , Sezgin Güzide Pelin , Kaplan Sema Sönmez
Published: December 2020

Background: This study aimed to assess the effect of a 980-nm diode laser following chemomechanical root canal preparation on the severity of post-operative pain (PP) after root canal treatment (RCT).Methods: This study included asymptomatic, single-rooted teeth with a periapical index (PAI) score of 3 or 4. All the patients received RCT, including dressing with calcium hydroxide (Ca(OH)2), during two visits. The patients were randomly divided into two groups (n:30): a control group, in which the final irrigation was performed using 5 ml of 2.5% sodium hypochlorite (NaOCI), followed by 5 ml of 17% and ethylenediaminetetraacetic acid (EDTA) and 5 ml of distilled water, and a laser group, in which the root canals were irradiated using a 980-nm diode laser after the final irrigation at both visits. The pain levels after both visits were evaluated using a visual analogue scale (VAS) after 8 h, 24 h, 48 h and 7 d. In addition, the time intervals to medication intake were recorded. The collected data were statistically analysed using the chi-square and Mann–Whitney U test (p<0.05).Results: The average pain level in the control group 24 h after the first visit was significantly higher than that in the laser group (p<0.05). The average pain level 24 h and 48 h after the second visit was significantly higher in the control group (p<0.05). The levels of PP 24 h after the first visit were higher than those after the second visit only in the control group (p<0.05). After the first visit, analgesic use in the control group was significantly higher after 8 h (40%) and 24 h (23%) as compared with that in the laser group (p<0.05).Conclusions: Root canal irradiation with a diode laser may reduce PP after RCT in single-rooted teeth with a PAI score of 3 or 4.Trial registration: Effect of the Diode Laser on Post-operative Pain After Endodontic Treatment in Teeth with Apical Periodontitis: NCT04486196. Registered 24 July 2020 - Retrospectively registered, http://clinicaltrials.gov/ct2/show/NCT04486196
Spatial-temporal patterns of malaria incidence in Uganda using HMIS data from 2015 to 2019
Authors: Kigozi Simon , Kigozi Ruth N , Sebuguzi Catherine M , Cano Jorge , Rutazaana Damian , Opigo Jimmy , Bousema Teun , Yeka Adoke , Gasasira Anne , Sartorius Benn , Pullan Rachel L
Published: December 2020

Background. As global progress to reduce malaria transmission continues, it is increasingly important to track changes in malaria incidence rather than prevalence. Risk estimates for Africa have largely underutilized available health management information systems (HMIS) data to monitor trends. This study uses national HMIS data, together with environmental and geographical data, to assess spatial-temporal patterns of malaria incidence at facility catchment level in Uganda, over a recent 5-year period.Methods. Data reported by 3446 health facilities in Uganda, between July 2015 and September 2019, was analysed. To assess the geographic accessibility of the health facilities network, AccessMod was employed to determine a three-hour cost-distance catchment around each facility. Using confirmed malaria cases and total catchment population by facility, an ecological Bayesian conditional autoregressive spatial-temporal Poisson model was fitted to generate monthly posterior incidence rate estimates, adjusted for caregiver education, rainfall, land surface temperature, night-time light (an indicator of urbanicity), and vegetation index.Results. An estimated 38.8 million (95% Credible Interval [CI]: 37.9 – 40.9) confirmed cases of malaria occurred over the period, with a national mean monthly incidence rate of 20.4 (95% CI: 19.9 - 21.5) cases per 1000, ranging from 8.9 (95% CI: 8.7 – 9.4) to 36.6 (95% CI: 35.7 – 38.5) across the study period. Strong seasonality was observed, with June-July experiencing highest peaks and February-March the lowest peaks. There was also considerable geographic heterogeneity in incidence, with health facility catchment relative risk during peak transmission months ranging from 0 to 50.5 (95% CI: 49.0 – 50.8) times higher than national average. Both districts and health facility catchments showed significant positive spatial autocorrelation; health facility catchments had global Moran’s I = 0.3 (p<0.001) and districts Moran’s I = 0.4 (p<0.001). Notably, significant clusters of high-risk health facility catchments were concentrated in Acholi, West Nile, Karamoja, and East Central – Busoga regions.Conclusion. Findings showed clear countrywide spatial-temporal patterns with clustering of malaria risk across districts and health facility catchments within high risk regions, which can facilitate targeting of interventions to those areas at highest risk. Moreover, despite high and perennial transmission, seasonality for malaria incidence highlights the potential for optimal and timely implementation of targeted interventions.
Prognostic effect of increased left ventricular wall thickness in severe aortic stenosis
Authors: Park Kyungil , Park Tae-Ho , Jo Yoon-Seong , Cho Young-Rak , Park Jong-Sung , Kim Moo-Hyun , Kim Young-Dae
Published: December 2020

Background: It is unclear whether increased left ventricular (LV) thickness is associated with worse clinical outcomes in severe aortic stenosis (AS). The aim of this study was to determine the effect of increased LV wall thickness (LVWT) on major clinical outcomes in patients with severe AS.Methods and Results: This study included 290 severe AS patients (mean age 69.4 ± 11.0 years; 136 females) between January 2008 and December 2018. For outcome assessment, the endpoint was defined as death from all causes, cardiovascular death, and the aortic valve replacement (AVR) surgery rate. During follow-up (48.7 ± 39.0 months), 157 patients had AVR, 43 patients died, and 28 patients died from cardiovascular causes. Patients with increased LVWT underwent AVR surgery much more than those without LVWT (60.0% vs. 39.0%, p < 0.001). Furthermore, in patients with increased LVWT, the all-cause and cardiovascular death rates were significantly lower in the AVR group than in the non-AVR group (8.8% vs. 27.3%, p < 0.001, 4.8%, vs. 21.0%, p < 0.001). Multivariate analysis revealed that increased LVWT, age, dyspnea, and AVR surgery were significantly correlated with cardiovascular death. Conclusions: In patients with severe AS, increased LVWT was associated with a higher AVR surgery rate and an increased rate of cardiovascular death independent of other well-known prognostic variates. Thus, these findings suggest that increased LVWT might be used as a potential prognostic factor in severe AS patients.
Global Metabolomic and Lipidomic Analysis Reveals the Potential Mechanisms of Hemolysis Effect of Ophiopogonin D and Ophiopogonin D’ in vivo
Authors: Huan-Hua Xu , Jiang Zhen-Hong , Huang Cong-Shu , Sun Yu-Ting , Xu Long-Long , Tang Xiang-Ling , Tan Hong-Ling , Ma Zeng-Chun , Gao Yue
Published: December 2020

Background: OPD and OPD' are the two main active components of Ophiopogon japonicas in Shenmai injection (SMI). Being isomers of each other, they are supposed to have similar pharmacological activities, but the actual situation is complicated. The difference of hemolytic behavior between OPD and OPD' in vivo and in vitro was discovered and reported by our group for the first time. In vitro, only OPD' showed hemolysis reaction, while in vivo, both OPD and OPD' caused hemolysis. In vitro, the primary cause of hemolysis has been confirmed to be related to the difference between physical and chemical properties of OPD and OPD'. In vivo, although there is a possible explanation for this phenomenon, the one is that OPD is bio-transformed into OPD' or its analogues in vivo, the other one is that both OPD and OPD' were metabolized into more activated forms for hemolysis. However, the mechanism of hemolysis in vivo is still unclear, especially the existing literature are still difficult to explain why OPD shows the inconsistent hemolysis behavior in vivo and in vitro. Therefore, the study of hemolysis of OPD and OPD' in vivo is of great practical significance in response to the increase of adverse events of SMI.Methods: Aiming at the hemolysis in vivo, this manuscript adopted untargeted metabolomics and lipidomics technology to preliminarily explore the changes of plasma metabolites and lipids of OPD- and OPD'-treated rats. Metabolomics and lipidomics analyses were performed on ultra-high performance liquid chromatography (UPLC) system tandem with different mass spectrometers (MS) and different columns respectively. Multivariate statistical approaches such as principal component analysis (PCA) and orthogonal partial least square-discriminant analysis (OPLS-DA) were applied to screen the differential metabolites and lipids.Results: Both OPD and OPD' groups experienced hemolysis, Changes in endogenous differential metabolites and differential lipids, enrichment of differential metabolic pathways, and correlation analysis of differential metabolites and lipids all indicated that the causes of hemolysis by OPD and OPD' were closely related to the interference of phospholipid metabolism.Conclusions: This study provided a comprehensive description of metabolomics and lipidomics changes between OPD- and OPD'-treated rats, it would add to the knowledge base of the field, which also provided scientific guidance for the subsequent mechanism research. However, the underlying mechanism require further research.
The evaluation of annuloplasty in bicuspid aortic valve repair using cardiac magnetic resonance
Authors: Jasinski Marek , Miszalski-Jamka Karol , Kosiorowska Kinga , Gocol Radoslaw , Wenzel-Jasinska Izabella , Bielicki Grzegorz , Berezowski Mikolaj , Lukaszewski Marceli , Kansy Andrzej , Deja Marek
Published: December 2020

Background: The incompetent bicuspid aortic valve (BAV) can be replaced or repaired using various surgical techniques. This study sought to assess the efficacy of external annuloplasty and postoperative reverse remodelling using cardiac magnetic resonance (CMR) and compare the results of external and subcommissural annuloplasty. Methods: Out of a total of 200 BAV repair performed between 2004 and 2018, 21 consecutive patients (median age 54 years) with regurgitation requiring valve repair with annuloplasty without concomitant aortic root surgery were prospectively referred for CMR and transthoracic echocardiography (TTE) one year after the operation. Two aortic annulus stabilization techniques were used: external, circumferential annuloplasty (EA), and subcommissural annuloplasty (SCA). Results: 11 patients received EA and 10 patients were treated using SCA. There was no in-hospital mortality and all patients survived the follow-up period (median: 12.6 months (first quartile: 6.6; third quartile: 14.1). CMR showed strong correlation between postoperative aortic recurrent regurgitant fraction and left ventricular end-diastolic volume (r = 0.62; p = 0.003) as well as left ventricular ejection fraction (r = -0.53; p = 0.01). Patients treated with EA as compared with SCA had larger anatomic aortic valve area measured by CMR (3.5 (2.5; 4.0) vs. 2.5 cm2 (2.0; 3.4); p = 0.04). In both EA and SCA group, aortic valve area below 3.5 cm2 correlated with no regurgitation recurrency. EA (vs. SCA) was associated with lower peak transvalvular aortic gradients (10 (6; 17) vs. 21mmHg (15; 27); p = 0.04). Conclusions: The repair of the bicuspid aortic valve provides significant postoperative reverse remodelling, provided no recurrent regurgitation and durable reduction annuloplasty can be achieved. EA is associated with lower transvalvular gradients and higher aortic valve area assessed by CMR, compared to SCA.
Aquaporin 3 promotes human extravillous trophoblast migration and invasion
Authors: Nong Yingqi , Li Shifen , Liu Wenjuan , Zhang Xiqian , Fan Lin , Chen Ye , Huang Qianwen , Zhang Qianyu , Liu Fenghua
Published: December 2020

Problem: Does aquaporin 3 (AQP3) affect the migration and invasion of human extravillous trophoblast (HTR8/Svneo) cells?Method of Study: A lentivirus infection system was used to construct stable cell lines with either AQP3 knockdown or overexpression. RT-PCR and western blotting were used to verify the efficiencies of AQP3 knockdown or overexpression in HTR8/Svneo cells at mRNA and protein levels, respectively. Cell Counting Kit-8 and flow cytometry assays were used to detect the influence of AQP3 knockdown or overexpression on proliferation and apoptosis of HTR8/Svneo cells. In addition, wound healing and Transwell invasion assays were used to detect the effects of AQP3 knockdown or overexpression on migration and invasion capabilities of HTR8/Svneo cells. An Agilent gene chip was used to screen for significant differentially expressed genes after AQP3 knockdown. Finally, mechanisms by which AQP3 influences the migration and invasion of HTR8/Svneo cells were explored using bioinformatic analysis.Results: Compared with controls, migration and invasion capabilities of HTR8/Svneo cells were significantly reduced after AQP3 knockdown, and significantly increased after AQP3 overexpression. Subsequent bioinformatic analysis of gene chip expression profiles indicated downregulation of genes related to adhesion such as PDGF-B, as well as signaling pathways (such as PIK3/AKT, NF-κB, and TNF) after AQP3 knockdown. Conclusions: AQP3 could significantly promote migration and invasion capabilities of human extravillous trophoblasts, it may mediate embryo invasion and adhesion to endometrium by regulating PDGF-B, PIK3/AKT signaling pathways, although this requires further verification.
G6PD deficiency and severity of COVID19 pneumonia and acute respiratory distress syndrome: tip of the iceberg?
Authors: Youssef Jihad G. , Zahiruddin Faisal , Youssef George , Padmanabhan Sriram , Ensor Joe , Pingali Sai Ravi , Zu Youli , Sahay Sandeep , Iyer Swaminathan P.
Published: December 2020

The severe pneumonia caused by the human Coronavirus (hCoV)- SARS-CoV-2 has inflicted heavy casualties, especially among the elderly and those with co-morbid illnesses irrespective of their age. The high mortality in African-Americans and males, in general, raises the concern for a possible X-linked mediated process that could affect the viral pathogenesis and the immune system. We hypothesized that G6PD, the most common X linked enzyme deficiency associated with redox status, may have a role in severity of pneumonia. Retrospective chart review was performed in hospitalized patients with COVID19 pneumonia needing supplemental oxygen. A total of 17 patients were evaluated; six with G6PD deficiency (G6PDd), and 11 with normal levels. The two groups (Normal and G6PDd) were comparable in terms of age, sex and co-morbidities, and laboratory parameters-LDH, IL-6, CRP, and Ferritin, respectively. Thirteen patients needed ventilatory support with 8 in the normal group and 5 in the G6PDd group (72% vs.83%). The main differences indicating increasing severity in normal vs. G6PDd groups included G6PD levels (12.2 vs. 5.6, P=0.0002), PaO2/FiO2 ratio (159 vs. 108, P=0.05), days on mechanical ventilation (10.25 vs. 21 days P=0.04), hemoglobin level (10 vs. 8.1 P=0.03) and Hematocrit (32 vs. 26 P=0.015). Only one patient with G6PDd died; 16 were discharged home. Our clinical series ascribes a possible biological role for G6PDd in SARS-CoV2 viral proliferation. It is imperative that further studies are performed to understand the interplay between the viral and host factors in G6PDd that may lead to disparity in outcomes.
Beneficial effect of Indigo Naturalis on acute lung injury induced by influenza A virus
Authors: Tu Peng , Tian Rong , Lu Yan , Zhang Yunyi , Zhu Haiyan , Ling Lijun , Li Hong , Chen Daofeng
Published: December 2020

Background: Infections induced by influenza viruses, as well as coronavirus disease 19 (COVID-19) pandemic induced by severe acute respiratory coronavirus 2 (SARS-CoV-2) led to acute lung injury (ALI) and multi organ failure, during which traditional Chinese medicine (TCM) played an important role in treatment of the pandemic. The study aimed to investigate the effect of Indigo Naturalis on ALI induced by influenza A virus (IAV) in mice.Method: The anti-influenza and anti-inflammatory properties of aqueous extract of Indigo Naturalis (INAE) were evaluated in vitro. BALB/c mice inoculated intranasally with IAV (H1N1) were treated intragastrically with INAE (40, 80 and 160 mg·kg-1/d) 2 h later for 4 or 7 days. Animal lifespan and mortality were recorded. Expression of high mobility group box-1 protein (HMGB-1) and toll-like receptor 4 (TLR4) were evaluated through immunohistological staining. Inflammatory cytokines were also monitored by ELISA.Result: INAE inhibited virus replication on Madin-Darby canine kidney (MDCK) cells and decreased nitric oxide (NO) production from lipopolysaccharide (LPS)-stimulated peritoneal macrophages in vitro. The results showed that oral administration of 160 mg/kg of INAE significantly improved the lifespan (P < 0.01) and survival rate of IAV infected mice, improved lung injury and lowered viral replication in lung tissue (P < 0.01). Treatment with INAE (40, 80 and 160 mg/kg) significantly increased liver weight and liver index (P < 0.05), as well as weight and organ index of thymus and spleen at 160 mg/kg (P < 0.05). Serum alanine transaminase (ALT) and aspartate aminotransferase (AST) levels were reduced by INAE administration (P < 0.05). The expression of HMGB-1 and TLR4 in lung tissue were also suppressed. The increased production of myeloperoxidase (MPO) and methylene dioxyamphetamine (MDA) in lung tissue were inhibited by INAE treatment (P < 0.05). Treatment with INAE reduced the high levels of interferon α (IFN-α), interferon β (IFN-β), monocyte chemoattractant protein-1 (MCP-1), regulated upon activation normal T cell expressed and secreted factor (RANTES), interferon induced protein-10 (IP-10), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) (P < 0.05), with increased production of interferon γ (IFN-γ) and interleukin-10 (IL-10) (P < 0.05).Conclusion: The results showed that INAE alleviated IAV induced ALI in mice. The mechanisms of INAE were associated with its anti-influenza, anti-inflammatory and anti-oxidation properties. Indigo Naturalis might have clinical potential to treat ALI induced by IAV.
The Effect of Hatha Yoga on Low Back Pain and Sleep Quality in Nulliparous Pregnant Women: A Clinical Trial Study
Authors: namdar peyman , hoseini narges , dehghankar leila , yekefallah leili
Published: December 2020

Background“Sleep quality disorder” and “low back pain” are some of the most common complaints of pregnant women during pregnancy and disturb their daily activities. Currently, there are not enough interventions for these symptoms. Recently, the sport of yoga, one of the stretching sports and therapeutic methods, has attracted the attention of rehabilitation specialists. This study aimed to determine the effect of Hatha yoga on low back pain and sleep quality in nulliparous pregnant women.MethodsThis controlled clinical trial study was performed on 60 eligible nulliparous pregnant women at the gestation age of 24 to 28 weeks with normal pregnancy in the gynecology clinic of Kowsar Hospital in Qazvin city, Iran. The samples were selected using convenience sampling and were assigned to intervention and control groups via random sampling without replacement. In addition to receiving routine pregnancy care by referring to the gynecology clinic of the hospital, the intervention group attended Hatha yoga classes twice a week (each session lasting 75 minutes) at the Hatha yoga specialized sports club from week 26 to week 37 of their pregnancy. A demographic information questionnaire, a visual pain scale, and the Pittsburgh Sleep Quality Index were used to collect information. In addition, SPSS software (version 24) and descriptive and inferential statistics were used to analyze the data. The significance level of all the tests was considered to be p <0.05.ResultsUsing Wilcoxon tests, the comparison of low back pain in the intervention group before (with the p-value of 0.057) and after (with the p-value of 0.172) the study showed that there was no significant difference between the pain scores in the intervention group. Moreover, using Wilcoxon tests, the comparison of the sleep quality score in the intervention group before (with the p-value of 0.007) and after (with the p-value of 0.001) the study indicated that there was a significant difference in the sleep quality scores in the intervention group. ConclusionBased on the results of the study, it can be said that Hatha yoga did not have a significant effect on the low back pain scores in the intervention group, however, it had a significant effect on their sleep quality. According to the findings of this study, the correct and regular use of Hatha yoga under the supervision of a specialist instructor can be valuable for pregnant women in their second trimester due to its being non-invasiveness and applicable.Trial registrationThe clinical trial registration code for this study was obtained from the Iranian Registry of Clinical Trials on 19.02.2019 (IRCT code: IRCT20190919044819N1).
DIGITAL LITERATURE: A LITERARY TREND OF THE TWENTY FIRST CENTURY
Authors:   M.Phil., Scholar Professor of English., Rajathi J Rebecca , Kalamani S. ,   Avinashilingam Institute for Home Science and Higher Education for Women Coimbatore - 641043.
Published: December 2020

Literature has stood the test of time, though there were many changes in its form. It truly reflects, as a mirror, the happenings of the society. Literature in the twenty first century has a deep and far-reaching root in the social networks, impacts of environment studies in literature, and so on. It is influenced by the perspectives of how scholars engage and study literature in the present age. The twenty first century literature can collectively be classified under three types of literary writings, namely, informative literature, environmental literature and digital literature. The latest trend of the twenty first century is the study of literature through the digital platform, introduced during the postmodern era. This literature is created to promote the exchange of ideas and to increase easy access of literary works through e-books, blogs, webpages, including audio and graphics. The benefits of digital literature are easy accessibility and the digital contents are engaging and inspiring because of their interactivity. Moreover, online text and webpages are never out of stock. Key Words: Literature, digitisation, interactivity, society, demand.