bluuebunny/crossref_metadata_2025 huggingface dataset:
Anlotinib as a promising inhibitor on tumor growth of oral squamous cell carcinoma through cell apoptosis and mitotic catastrophe
Authors: Deng Zhaoming , Liao Wei , Wei Wei , Zhong Guihua , He Chao , Zhang Hongbo , Liu Qiaodan , Xu Xiwei , Liang Jun , Liu Zhigang
Published: January 2021

Background

Oral squamous cell carcinoma (OSCC) has been one of the most malignant cancers in head and neck region. Anlotinib is a tyrosine kinase inhibitor targeting several receptors such as vascular endothelial growth factor receptor (VEGFR), fibroblast growth factor receptor (FGFR), platelet-derived growth factor receptor (PDGFR) and c-Kit. Here we investigated whether Anlotinib have any antitumor effect on oral cancer and tried to explore and explain the possible mechanism.

Methods

Data from The Cancer Genome Atlas and the Gene Expression Omnibus and Gene Expression Omnibus database was collected to analyze the relationship between the expression of vascular epithelial growth factor receptor 2 and the overall survival rate of OSCC. Oral cancer cell lines Cal-27 and SCC-25 were cultured to conduct all the experiments. In vitro experiments such as CCK-8, colony formation, cell cycle assay and cell apoptosis assay were conducted to detect cell proliferation ability and the change of cell phase and apoptosis. Proteins concerning cell cycle and cell apoptosis were visualized via western blot. α-Tubulin were visualized via immunofluorescence to detect cells undergoing mitotic catastrophe.

Results

Higher expression of VEGFR-2 was significantly related to poorer prognosis. Experiment in vitro demonstrated that cell proliferation was significantly inhibited(p < 0.05) after Anlotinib administration and G2/M arrest and apoptosis were both detected in both cell lines. Cycle-related proteins promoting cell cycle progression and proteins related to cell survival were downregulated in Anlotinib group compared to the control group. Cell-death-related biomarker and phosphorylated histone 3 were upregulated in expression in Anlotinib group. Abnormal spindle apparatus was observed in cells undergoing mitotic catastrophe.

Conclusions

Anlotinib could exert an antitumor effect on oral cancer cell lines via apoptotic pathway and mitotic catastrophe pattern, presenting a promising potential therapy for patients with OSCC.
Drug resistance markers within an evolving efficacy of anti-malarial drugs in Cameroon: a systematic review and meta-analysis (1998–2020)
Authors: Niba Peter Thelma Ngwa , Nji Akindeh M. , Evehe Marie-Solange , Ali Innocent M. , Netongo Palmer Masumbe , Ngwafor Randolph , Moyeh Marcel N. , Ngum Lesley Ngum , Ndum Oliva Ebie , Acho Fon Abongwa , Mbu’u Cyrille Mbanwi , Fosah Dorothy A. , Atogho-Tiedeu Barbara , Achonduh-Atijegbe Olivia , Djokam-Dadjeu Rosine , Chedjou Jean Paul Kengne , Bigoga Jude D. , Moukoko Carole Else Eboumbou , Ajua Anthony , Achidi Eric , Tallah Esther , Leke Rose G. F. , Tourgordi Alexis , Ringwald Pascal , Alifrangis Michael , Mbacham Wilfred F.
Published: January 2021

Background

Malaria remains highly endemic in Cameroon. The rapid emergence and spread of drug resistance was responsible for the change from monotherapies to artemisinin-based combinations. This systematic review and meta-analysis aimed to determine the prevalence and distribution of Plasmodium falciparum drug resistance markers within an evolving efficacy of anti-malarial drugs in Cameroon from January 1998 to August 2020.

Methods

The PRISMA-P and PRISMA statements were adopted in the inclusion of studies on single nucleotide polymorphisms (SNPs) of P. falciparum anti-malarial drug resistance genes (Pfcrt, Pfmdr1, Pfdhfr, Pfdhps, Pfatp6, Pfcytb and Pfk13). The heterogeneity of the included studies was evaluated using the Cochran’s Q and I2 statistics. The random effects model was used as standard in the determination of heterogeneity between studies.

Results

Out of the 902 records screened, 48 studies were included in this aggregated meta-analysis of molecular data. A total of 18,706 SNPs of the anti-malarial drug resistance genes were genotyped from 47,382 samples which yielded a pooled prevalence of 35.4% (95% CI 29.1–42.3%). Between 1998 and 2020, there was significant decline (P < 0.0001 for all) in key mutants including Pfcrt 76 T (79.9%-43.0%), Pfmdr1 86Y (82.7%-30.5%), Pfdhfr 51I (72.2%-66.9%), Pfdhfr 59R (76.5%-67.8%), Pfdhfr 108 N (80.8%-67.6%). The only exception was Pfdhps 437G which increased over time (30.4%-46.9%, P < 0.0001) and Pfdhps 540E that remained largely unchanged (0.0%-0.4%, P = 0.201). Exploring mutant haplotypes, the study observed a significant increase in the prevalence of Pfcrt CVIET mixed quintuple haplotype from 57.1% in 1998 to 57.9% in 2020 (P < 0.0001). In addition, within the same study period, there was no significant change in the triple Pfdhfr IRN mutant haplotype (66.2% to 67.3%, P = 0.427). The Pfk13 amino acid polymorphisms associated with artemisinin resistance were not detected.

Conclusions

This review reported an overall decline in the prevalence of P. falciparum gene mutations conferring resistance to 4-aminoquinolines and amino alcohols for a period over two decades. Resistance to artemisinins measured by the presence of SNPs in the Pfk13 gene does not seem to be a problem in Cameroon.

Systematic review registration PROSPERO CRD42020162620
Persistence of mRNA indicative of Plasmodium falciparum ring-stage parasites 42 days after artemisinin and non-artemisinin combination therapy in naturally infected Malians
Authors: Mahamar Almahamoudou , Lanke Kjerstin , Graumans Wouter , Diawara Halimatou , Sanogo Koualy , Diarra Kalifa , Niambele Sidi Mohamed , Gosling Roly , Drakeley Chris , Chen Ingrid , Dicko Alassane , Bousema Teun , Roh Michelle E.
Published: January 2021

Background

Malaria control in sub-Saharan Africa relies upon prompt case management with artemisinin-based combination therapy (ACT). Ring-stage parasite mRNA, measured by sbp1 quantitative reverse-transcriptase PCR (qRT-PCR), was previously reported to persist after ACT treatment and hypothesized to reflect temporary arrest of the growth of ring-stage parasites (dormancy) following exposure to artemisinins. Here, the persistence of ring-stage parasitaemia following ACT and non-ACT treatment was examined.

Methods

Samples were used from naturally infected Malian gametocyte carriers who received dihydroartemisinin–piperaquine (DP) or sulfadoxine–pyrimethamine (SP–AQ) with or without gametocytocidal drugs. Gametocytes and ring-stage parasites were quantified by qRT-PCR during 42 days of follow-up.

Results

At baseline, 89% (64/73) of participants had measurable ring-stage parasite mRNA. Following treatment, the proportion of ring-stage parasite-positive individuals and estimated densities declined for all four treatment groups. Ring-stage parasite prevalence and density was generally lower in arms that received DP compared to SP–AQ. This finding was most apparent days 1, 2, and 42 of follow-up (p < 0.01). Gametocytocidal drugs did not influence ring-stage parasite persistence. Ring-stage parasite density estimates on days 14 and 28 after initiation of treatment were higher among individuals who subsequently experienced recurrent parasitaemia compared to those who remained free of parasites until day 42 after initiation of treatment (pday 14 = 0.011 and pday 28 = 0.068). No association of ring-stage persistence with gametocyte carriage was observed.

Conclusions

The current findings of lower ring-stage persistence after ACT without an effect of gametocytocidal partner drugs affirms the use of sbp1 as ring-stage marker. Lower persistence of ring-stage mRNA after ACT treatment suggests the marker may not reflect dormant parasites whilst it was predictive of re-appearance of parasitaemia.
Impact of placental malaria on maternal, placental and fetal cord responses and its role in pregnancy outcomes in women from Blue Nile State, Sudan
Authors: Omer Samia , Franco-Jarava Clara , Noureldien Ali , Omer Mona , Abdelrahim Mutasim , Molina Israel , Adam Ishag
Published: January 2021

Background

The sequestration ofPlasmodium falciparuminfected cells in the placenta results in placental malaria (PM). It activates the mother's immune cells and induces secretion of inflammatory cytokines, which might influence pregnancy outcomes. This study aims to investigate the cytokines (levels IL-4, IL-6, IL-10, IL-17A, and INF γ) in maternal peripheral, placental, and umbilical cord blood in response to PM and the extent to which this may influence maternal haemoglobin levels and birth weight.

Methods

A total of 185 consenting Sudanese women from Blue Nile State were enrolled at delivery time in a cross-sectional study conducted between Jan 2012-Dec 2015. Malaria infection in the collected maternal peripheral, placental, umbilical cord samples was determined microscopically, and ELISA was used to measure the plasma levels IL-4, IL-6, IL-10, IL-17A, and INF γ in the collected positive and negative malaria samples.

Results

Elevated levels of IL-4 and IL-10 and reduced levels of IL-6 were detected in the malaria positive samples in comparison to the negative ones in the three types of the samples investigated. Maternal, IL-4 and IL-10 were significantly higher in the samples collected from the PM infected group compared to the non-infected control (P < 0.001). While the absence of PM was significantly associated with the IL-6 and maternal IFN-γ levels, maternal IL-17A, placental and umbilical cord IFN-γ levels showed no significant difference (P = 0.214, P = 0.065, P = 0.536, respectively) due to infection. Haemoglobin level and birth weight were increased in the group with high levels of IL-6 and IL-17A, but not in the group with IL-4 and IL-10 levels. While significantly negative correlation was found between IFN-γ levels and birth weight for all three types of samples, only maternal peripheral IFN-γ level was significantly positively correlated with maternal haemoglobin (r = 0.171, P = 0.020).

Conclusion

These results suggest that PM induces mother’s immune response and impairs her cytokine profile, which might alter maternal haemoglobin levels and the baby's birth weight.
Comparison of left atrial and left atrial appendage mechanics in the risk stratification of stroke in patients with atrial fibrillation
Authors: Mao Yankai , Yu Chan , Yang Yuan , Ma Mingming , Wang Yunhe , Jiang Ruhong , Chen Ran , Zhao Bowen , Jiang Chenyang
Published: January 2021

Background

Left atrial (LA) and left atrial appendage (LAA) dysfunction has been demonstrated to contribute to atrial fibrillation (AF)-related stroke. However, usefulness of LA and LAA mechanics has not been fully compared. We sought to investigate the association of LA and LAA mechanics with stroke and to compare their diagnostic values in the risk stratification of stroke in patients with nonvalvular AF.

Methods

A total of 208 consecutive patients with AF (63.58 ± 10.37 years, 63.9% male,57.7% persistent AF) who underwent echocardiography before catheter ablation were prospectively enrolled. Speckle-tracking was used to measure LA and LAA global longitudinal strain (GLS). LA and LAA mechanical dispersions (MD) were defined as the standard deviation (SD) of time to peak positive strain corrected by the R-R interval.

Results

Patients with prior stroke/ transient ischemic attack (TIA) (n = 31) had significantly higher LA and LAA MD than those without (n = 177) (11.56 ± 4.38% vs. 8.43 ± 3.44%, 15.15 ± 5.46% vs. 10.94 ± 4.40%, both P < 0.01). In multivariable analysis, LA and LAA MD were independently associated with stroke/TIA (odds ratio, 1.18–1.29, 1.19–1.22, respectively, both P < 0.01), providing incremental values over clinical and standard echocardiographic parameters. In a subgroup analysis, LA MD was more useful than LAA MD in patients with normal LA volumes, while LAA MD was superior to LA MD in patients with LA enlargement.

Conclusions

Higher LA and LAA mechanical dispersion are independently associated with stroke/TIA in AF patients and had incremental values over clinical and conventional echocardiographic parameters. What’s more, priorities of dispersion assessment are different depending on patients’ LA size.
Usefulness of speckle tracking echocardiography and biomarkers for detecting acute cellular rejection after heart transplantation
Authors: Cruz Cecilia Beatriz Bittencourt Viana , Hajjar Ludhmila A. , Bacal Fernando , Lofrano-Alves Marco S. , Lima Márcio S. M. , Abduch Maria C. , Vieira Marcelo L. C. , Chiang Hsu P. , Salviano Juliana B. C. , da Silva Costa Isabela Bispo Santos , Fukushima Julia Tizue , Sbano Joao C. N. , Mathias Wilson , Tsutsui Jeane M.
Published: January 2021

Background

Acute cellular rejection (ACR) is a major complication after heart transplantation. Endomyocardial biopsy (EMB) remains the gold standard for its diagnosis, but it has concerning complications. We evaluated the usefulness of speckle tracking echocardiography (STE) and biomarkers for detecting ACR after heart transplantation.

Methods

We prospectively studied 60 transplant patients with normal left and right ventricular systolic function who underwent EMB for surveillance 6 months after transplantation. Sixty age- and sex-matched healthy individuals constituted the control group. Conventional echocardiographic parameters, left ventricular global longitudinal, radial and circumferential strain (LV-GLS, LV-GRS and LV-GCS, respectively), left ventricular systolic twist (LV-twist) and right ventricular free wall longitudinal strain (RV-FWLS) were analyzed just before the procedure. We also measured biomarkers at the same moment.

Results

Among the 60 studied patients, 17 (28%) had severe ACR (grade ≥ 2R), and 43 (72%) had no significant ACR (grade 0 – 1R). The absolute values of LV-GLS, LV-twist and RV-FWLS were lower in transplant patients with ACR degree ≥ 2 R than in those without ACR (12.5% ± 2.9% vs 14.8% ± 2.3%, p=0.002; 13.9° ± 4.8° vs 17.1° ± 3.2°, p=0.048; 16.6% ± 2.9% vs 21.4%± 3.2%, p < 0.001; respectively), while no differences were observed between the LV-GRS or LV-GCS. All of these parameters were lower in the transplant group without ACR than in the nontransplant control group, except for the LV-twist. Cardiac troponin I levels were significantly higher in patients with significant ACR than in patients without significant ACR [0.19 ng/mL (0.09–1.31) vs 0.05 ng/mL (0.01–0.18), p=0.007]. The combination of troponin with LV-GLS, RV-FWLS and LV-Twist had an area under curve for the detection of ACR of 0.80 (0.68–0.92), 0.89 (0.81–0.93) and 0.79 (0.66–0.92), respectively.

Conclusion

Heart transplant patients have altered left ventricular dynamics compared with control individuals. The combination of troponin with strain parameters had higher accuracy for the detection of ACR than the isolated variables and this association might select patients with a higher risk for ACR who will benefit from an EMB procedure in the first year after heart transplantation.
Development of an M cell targeted nanocomposite system for effective oral protein delivery: preparation, in vitro and in vivo characterization
Authors: Song Jae Geun , Lee Sang Hoon , Han Hyo-Kyung
Published: January 2021

Background

There is a strong need for non-invasive and patient-friendly delivery systems of protein drugs for long-term therapy. However, oral delivery of protein drugs is a big challenge due to many barriers including instability in the gastrointestinal (GI) tract and low permeability. To overcome the absorption barriers in GI tract and improve the patient compliance, this study aimed to develop an M cell targeted-nanocomposite delivery system of protein drugs.

Results

An aminoclay-protein core complex (AC-Ins) was prepared by using insulin as a model protein and then sequentially coated with Ulex europaeus agglutinin 1 (UEA-1) for M-cell targeting and the pH sensitive polymer, Eudragit® L100 (EUAC-Ins). All nanoparticles were obtained with a high entrapment efficiency (> 90%) and their structural characteristics were confirmed by Fourier transform-infrared spectroscopy, energy dispersive X-ray spectroscopy, and circular dichroism. Among the developed nanoparticles, EUAC-Ins effectively suppressed drug release at pH 1.2, while rapidly released drugs at pH 6.8 due to dissolution of the outer coating layer. The conformational stability of insulin entrapped in EUAC-Ins was well maintained in the presence of proteolytic enzymes. Compared to free insulin, EUAC-Ins increased the membrane transport of insulin by 4.4-fold in M cells. In parallel, oral administration of EUAC-Ins in mice enhanced insulin uptake by 4.1-fold in the intestinal Peyer’s patches and 2.6-fold in intestinal epithelium tissues with normal villi, compared to free insulin. Orally administered EUAC-Ins decreased significantly the blood glucose level in diabetic mice, while the effect of oral insulin solution was negligible.

Conclusion

An M cell targeted-ternary nanocomposite system obtained by dual coating of the aminoclay-protein core complex with UEA-1 and a pH dependent polymer is promising as an effective oral protein delivery carrier.
Double attack strategy for leukemia using a pre-targeting bispecific antibody (CD20 Ab-mPEG scFv) and actively attracting PEGylated liposomal doxorubicin to enhance anti-tumor activity
Authors: Ho Kai-Wen , Chen I.-J.u , Cheng Yi-An , Liao Tzu-Yi , Liu En-Shuo , Chen Huei-Jen , Lu Yun-Chi , Su Yu-Cheng , Roffler Steve R. , Huang Bo-Cheng , Liu Hui-Ju , Huang Ming-Yii , Chen Chiao-Yun , Cheng Tian-Lu
Published: January 2021

Background

Tumor-targeted nanoparticles hold great promise as new tools for therapy of liquid cancers. Furthermore, the therapeutic efficacy of nanoparticles can be improved by enhancing the cancer cellular internalization.

Methods

In this study, we developed a humanized bispecific antibody (BsAbs: CD20 Ab-mPEG scFv) which retains the clinical anti-CD20 whole antibody (Ofatumumab) and is fused with an anti-mPEG single chain antibody (scFv) that can target the systemic liquid tumor cells. This combination achieves the therapeutic function and simultaneously “grabs” Lipo-Dox® (PEGylated liposomal doxorubicin, PLD) to enhance the cellular internalization and anticancer activity of PLD.

Results

We successfully constructed the CD20 Ab-mPEG scFv and proved that CD20 Ab-mPEG scFv can target CD20-expressing Raji cells and simultaneously grab PEGylated liposomal DiD increasing the internalization ability up to 60% in 24 h. We further showed that the combination of CD20 Ab-mPEG scFv and PLD successfully led to a ninefold increase in tumor cytotoxicity (LC50: 0.38 nM) compared to the CD20 Ab-DNS scFv and PLD (lC50: 3.45 nM) in vitro. Importantly, a combination of CD20 Ab-mPEG scFv and PLD had greater anti-liquid tumor efficacy (P = 0.0005) in Raji-bearing mice than CD20 Ab-DNS scFv and PLD.

Conclusion

Our results indicate that this “double-attack” strategy using CD20 Ab-mPEG scFv and PLD can retain the tumor targeting (first attack) and confer PLD tumor-selectivity (second attack) to enhance PLD internalization and improve therapeutic efficacy in liquid tumors.
Networks of stress, affect and eating behaviour: anticipated stress coping predicts goal-congruent eating in young adults
Authors: Pannicke Björn , Kaiser Tim , Reichenberger Julia , Blechert Jens
Published: January 2021

Background

Many people aim to eat healthily. Yet, affluent food environments encourage consumption of energy dense and nutrient-poor foods, making it difficult to accomplish individual goals such as maintaining a healthy diet and weight. Moreover, goal-congruent eating might be influenced by affects, stress and intense food cravings and might also impinge on these in turn. Directionality and interrelations of these variables are currently unclear, which impedes targeted intervention. Psychological network models offer an exploratory approach that might be helpful to identify unique associations between numerous variables as well as their directionality when based on longitudinal time-series data.

Methods

Across 14 days, 84 diet-interested participants (age range: 18–38 years, 85.7% female, mostly recruited via universities) reported their momentary states as well as retrospective eating episodes four times a day. We used multilevel vector autoregressive network models based on ecological momentary assessment data of momentary affects, perceived stress and stress coping, hunger, food craving as well as goal-congruent eating behaviour.

Results

Neither of the momentary measures of stress (experience of stress or stress coping), momentary affects or craving uniquely predicted goal-congruent eating. Yet, temporal effects indicated that higher anticipated stress coping predicted subsequent goal-congruent eating. Thus, the more confident participants were in their coping with upcoming challenges, the more they ate in line with their goals.

Conclusion

Most eating behaviour interventions focus on hunger and craving alongside negative and positive affect, thereby overlooking additional important variables like stress coping. Furthermore, self-regulation of eating behaviours seems to be represented by how much someone perceives a particular eating episode as matching their individual eating goal. To conclude, stress coping might be a potential novel intervention target for eating related Just-In-Time Adaptive Interventions in the context of intensive longitudinal assessment.
Process evaluations of early childhood obesity prevention interventions delivered via telephone or text messages: a systematic review
Authors: Ekambareshwar Mahalakshmi , Ekambareshwar Swathi , Mihrshahi Seema , Wen Li Ming , Baur Louise A. , Laws Rachel , Taki Sarah , Rissel Chris
Published: January 2021

Background

Increasingly, public health interventions are delivered via telephone and/or text messages. Recent systematic reviews of early childhood obesity prevention interventions have not adequately reported on the way interventions are delivered and the experiences/perceptions of stakeholders. We aimed to summarise the literature in early childhood obesity prevention interventions delivered via telephone or text messages for evidence of application of process evaluation primarily to evaluate stakeholders’ acceptability of interventions.

Methods

A systematic search of major electronic databases was carried out using the Population, Intervention, Comparison, Outcomes framework. Studies were included if interventions were delivered via telephone/text messages; aimed at changing caregivers’ behaviours to prevent early childhood obesity; with one or more outcomes related to early obesity risk factors such as breastfeeding, solid feeding, tummy time, sleep and settling, physical activity and screen time; published from inception to May 2020. All eligible studies were independently assessed by two reviewers using the Cochrane Collaboration tool for assessing risk of bias. Qualitative studies were assessed using the Consolidated Criteria for Reporting Qualitative Research and Standards for Reporting Qualitative Research tools.

Results

Twenty-four studies were eligible, and the overall risk of bias was low. Eight studies (33%) had evidence of process evaluation that examined participants’ perceptions of interventions. Participants appreciated the convenience of receiving interventions via telephone or text messages. 63% of all studies in this review showed improvement in one or more behaviours related to childhood obesity prevention. Participants were likely to modify behaviours if they received information from a credible source such as from health professionals.

Conclusion

There is limited reporting of stakeholders’ experiences in early obesity prevention studies delivered by telephone or text messages. Only one-third of studies examined participants’ acceptability and the potential for delivery of childhood obesity prevention interventions conveniently using this mode of delivery. Interventions delivered remotely via telephone or text messages have the potential to reach equal or a greater number of participants than those delivered via face-to-face methods. Future research should build in process evaluation alongside effectiveness measurements to provide important insight into intervention reach, acceptability and to inform scale up.

Trial registration

PROSPERO registration: CRD42019108658
Trends and factors associated with modification or discontinuation of the initial antiretroviral regimen during the first year of treatment in the Turkish HIV-TR Cohort, 2011–2017
Authors:   on behalf of the HIV-TR Study Group, Korten Volkan , Gökengin Deniz , Eren Gülhan , Yıldırmak Taner , Gencer Serap , Eraksoy Haluk , Inan Dilara , Kaptan Figen , Dokuzoğuz Başak , Karaoğlan Ilkay , Willke Ayşe , Gönen Mehmet , Ergönül Önder
Published: January 2021

Background

There is limited evidence on the modification or stopping of antiretroviral therapy (ART) regimens, including novel antiretroviral drugs. The aim of this study was to evaluate the discontinuation of first ART before and after the availability of better tolerated and less complex regimens by comparing the frequency, reasons and associations with patient characteristics.

Methods

A total of 3019 ART-naive patients registered in the HIV-TR cohort who started ART between Jan 2011 and Feb 2017 were studied. Only the first modification within the first year of treatment for each patient was included in the analyses. Reasons were classified as listed in the coded form in the web-based database. Cumulative incidences were analysed using competing risk function and factors associated with discontinuation of the ART regimen were examined using Cox proportional hazards models and Fine-Gray competing risk regression models.

Results

The initial ART regimen was discontinued in 351 out of 3019 eligible patients (11.6%) within the first year. The main reason for discontinuation was intolerance/toxicity (45.0%), followed by treatment simplification (9.7%), patient willingness (7.4%), poor compliance (7.1%), prevention of future toxicities (6.0%), virologic failure (5.4%), and provider preference (5.4%). Non-nucleoside reverse transcriptase inhibitor (NNRTI)-based (aHR = 4.4, [95% CI 3.0–6.4]; p < 0.0001) or protease inhibitor (PI)-based regimens (aHR = 4.3, [95% CI 3.1–6.0]; p < 0.0001) relative to integrase strand transfer inhibitor (InSTI)-based regimens were significantly associated with ART discontinuation. ART initiated at a later period (2015-Feb 2017) (aHR = 0.6, [95% CI 0.4–0.9]; p < 0.0001) was less likely to be discontinued. A lower rate of treatment discontinuation for intolerance/toxicity was observed with InSTI-based regimens (2.0%) than with NNRTI- (6.6%) and PI-based regimens (7.5%) (p < 0.001). The percentage of patients who achieved HIV RNA < 200 copies/mL within 12 months of ART initiation was 91% in the ART discontinued group vs. 94% in the continued group (p > 0.05).

Conclusion

ART discontinuation due to intolerance/toxicity and virologic failure decreased over time. InSTI-based regimens were less likely to be discontinued than PI- and NNRTI-based ART.
Titanium dioxide nanoparticles impair the inner blood-retinal barrier and retinal electrophysiology through rapid ADAM17 activation and claudin-5 degradation
Authors: Chan Yen-Ju , Liao Po-Lin , Tsai Chi-Hao , Cheng Yu-Wen , Lin Fan-Li , Ho Jau-Der , Chen Ching-Yi , Li Ching-Hao
Published: January 2021

Background

Depending on their distinct properties, titanium dioxide nanoparticles (TiO2-NPs) are manufactured extensively and widely present in our daily necessities, with growing environmental release and public concerns. In sunscreen formulations, supplementation of TiO2-NPs may reach up to 25% (w/w). Ocular contact with TiO2-NPs may occur accidentally in certain cases, allowing undesirable risks to human vision. This study aimed to understand the barrier integrity of retinal endothelial cells in response to TiO2-NP exposure. bEnd.3 cells and human retinal endothelial cells (HRECs) were exposed to TiO2-NP, followed by examination of their tight junction components and functions.

Results

TiO2-NP treatment apparently induced a broken structure of the junctional plaques, conferring decreased transendothelial electrical resistance, a permeable paracellular cleft, and improved cell migration in vitro. This might involve rapid activation of metalloproteinase, a disintegrin and metalloproteinase 17 (ADAM17), and ADAM17-mediated claudin-5 degradation. For the in vivo study, C57BL/6 mice were administered a single dose of TiO2-NP intravitreally and then subjected to a complete ophthalmology examination. Fluorescein leakage and reduced blood flow at the optical disc indicated a damaged inner blood-retinal barrier induced by TiO2-NPs. Inappreciable change in the thickness of retinal sublayers and alleviated electroretinography amplitude were observed in the TiO2-NP-treated eyes.

Conclusions

Overall, our data demonstrate that TiO2-NP can damage endothelial cell function, thereby affecting retinal electrophysiology.
Primary dedifferentiated Liposarcoma of vagina: a first case report
Authors: Xie Chuan , Shen Yangmei
Published: January 2021

Background

Dedifferentiated liposarcoma, one of the most deadly types of soft tissue sarcoma, is an aggressive and high-grade form of liposarcoma. Liposarcoma occurs most commonly in the retroperitoneum, extremities and trunk, but less frequently in the female genital tract. The vagina is a very rare site of origin. Herein we report the first case of dedifferentiated Liposarcoma deriving from vagina and discuss its clinical course.

Case presentation

A 38-year-old female patient presented to our institution with a painless vaginal mass. Abdominal computed tomography showed a 17.6 cm× 10.4 cm solid mass originating from the right lateral wall of her vagina. Then she underwent complete surgical resection of the tumor mass, and postoperative pathological result confirmed the diagnosis of dedifferentiated liposarcoma deriving from vagina. Six courses of combination chemotherapy with pirarubicin plus ifosfamide were performed after surgery. The patient remains with no evidence of disease recurrence with 13 months of follow-up.

Conclusions

Liposarcoma is very rare in female genital tract, and more rare for dedifferentiated liposarcoma in gynecologic field. Little is known about the clinical characteristics, pathological diagnosis, prognosis and optimal management strategy of vaginal dedifferentiated liposarcoma. Complete surgical resection followed by systemic chemotherapy is suggested to be standard treatment for dedifferentiated liposarcoma. Combination chemotherapy with pirarubicin and ifosfamide may be effective for treating vaginal dedifferentiated liposarcoma.
A novel surgical approach and technique and short-term clinical efficacy for the treatment of proximal humerus fractures with the combined use of medial anatomical locking plate fixation and minimally invasive lateral locking plate fixation
Authors: Wang Fu , Wang Yan , Dong Jinye , He Yu , Li Lianxin , Liu Fanxiao , Dong Jinlei
Published: January 2021

Background and hypothesis

The typical anterolateral approach is widely used to treat proximal humerus fractures with lateral locking fixation. However, lateral fixation cannot completely avoid medial reduction loss and varus deformity especially in the cases of an unstable medial column. We present a novel medial surgical approach and technique together with a minimally invasive lateral locking plate to fix proximal humerus fractures with an unstable medial column.

Materials and methods

We performed an anatomical study and reported 8 cases of proximal humerus fractures with unstable medial columns treated with plate fixation through a minimally invasive anterolateral approach and medial approach. All surgeries were performed by the same single surgeon. Patients were followed clinically and radiographically at 1, 3, 6, and 12 months postoperatively.

Results

There was a safe region located at the medial part of the proximal humerus just beneath the articular surface. An anatomical medial locking proximal humerus plate could be placed in the medial column and did not affect the axillary nerve, blood supply of the humeral head, or stability of the shoulder joint. Successful fracture healing was achieved in all 8 cases. The function and range of motion of the shoulder joint were satisfactory 24 months postoperatively, with an average Constant score (CS) of 82.8. No reduction loss (≥ 10° in any direction), screw cutout, nonunion, or deep infection occurred.

Conclusions

The combined application of medial anatomical locking plate fixation and minimally invasive lateral locking plate fixation is effective in maintaining operative reduction and preventing varus collapse and implant failure in proximal humerus fractures with an unstable medial column.
Influence of K-line on intraoperative and hidden blood loss in patients with ossification of the posterior longitudinal ligament when undergoing unilateral open-door laminoplasty
Authors: Li Yipeng , Li Jia , Wang Feng , Wang Linfeng , Shen Yong
Published: January 2021

Background

The K-line is a virtual straight line that connects the midpoints of the anteroposterior spinal canal diameter from C2 to C7 on a cervical lateral X-ray film. Patients with cervical ossification of the posterior longitudinal ligament (OPLL), in which the peak of the OPLL exceeds the K-line (K-line [-]), are less likely to experience sufficient decompression after laminoplasty compared with patients for whom the OPLL does not exceed the K-line (K-line [+]). This retrospective study investigated the influence of K-line position relative to the OPLL on intraoperative and hidden blood loss during unilateral open-door laminoplasty for OPLL.

Methods

Data were retrospectively analyzed of 108 patients with OPLL who underwent unilateral open-door laminoplasty between April 2015 and March 2018. Patient cases were categorized as K-line (+) or (-). The evaluated perioperative parameters were haematocrit, haemoglobin, intraoperative and hidden blood loss, surgical time, postoperative drainage, and complications. Radiological parameters included ossification occupancy ratio and C2-7 lordosis.

Results

The K-line (+) and K-line (-) groups were statistically comparable with regard to age, gender, body mass index, OPLL classification, medication history, C2-7 lordosis, postoperative haemoglobin and haematocrit, postoperative drainage, hidden blood loss, and complications. The occupying ratio of the K-line (-) group was significantly greater than that of the K-line (+) group (49.5 ± 15.3% cf. 42.3 ± 10.1%; P = 0.006), and the intraoperative blood loss was also significantly higher (286 ± 110.5 mL cf. 205.5 ± 98.3 L, P = 0.003). The hidden blood loss of the K-line (-) group was higher than that of the K-line (+), but not significantly (295.5 ± 112.6 mL cf. 265.6 ± 103.8 mL; P = 0.072).

Conclusion

Intraoperative and hidden blood loss associated with unilateral open-door laminoplasty can be predicted by the spatial relationship of the K-line and osteophyte. This relationship is a simple and practical index that may help surgeons determine the appropriate surgical strategy for patients with OPLL.
A new UHPLC-MS/MS method for the screening of urinary oligosaccharides expands the detection of storage disorders
Authors: Semeraro Michela , Sacchetti Elisa , Deodato Federica , Coşkun Turgay , Lay Incilay , Catesini Giulio , Olivieri Giorgia , Rizzo Cristiano , Boenzi Sara , Dionisi-Vici Carlo
Published: January 2021

Background

Oligosaccharidoses are storage disorders due to enzymatic defects involved in the breakdown of the oligosaccharidic component of glycosylated proteins. The defect cause the accumulation of oligosaccharides (OS) and, depending on the lacking enzyme, results in characteristic profiles which are helpful for the diagnosis. We developed a new tandem mass spectrometry method for the screening of urinary OS which was applied to identify a large panel of storage disorders.

Methods

The method was set-up in urine and dried urine spots (DUS). Samples were analysed, without derivatization and using maltoheptaose as internal standard, by UHPLC-MS/MS with MRM acquisition of target OS transitions, including Glc4, the biomarker of Pompe disease. The chromatographic run was < 30 min. Samples from patients with known storage disorders were used for clinical validation.

Results

The method allowed to confirm the diagnosis of oligosaccharidoses (sialidosis, α-/β-mannosidosis, fucosidosis, aspartylglucosaminuria) and of GM1 and GM2 (Sandhoff type) gangliosidosis, by detecting specific OS profiles. In other storage disorders (mucolipidosis II and III, mucopolysaccharidosis type IVB) the analyisis revealed abnormal OS excretion with non-specific profiles. Besides Pompe disease, the tetrasaccharide Glc4 was increased also in disorders of autophagy (Vici syndrome, Yunis-Varon syndrome, and Danon disease) presenting cardiomuscular involvement with glycogen storage. Overall, results showed a clear separation between patients and controls, both in urine and in DUS.

Conclusion

This new UHPLC/MS-MS method, which is suitable for rapid and easy screening of OS in urine and DUS, expands the detection of storage disorders from oligosaccharidoses to other diseases, including the novel category of inherited disorders of autophagy.
Malnutrition as the cause of recumbency in suckler cows associated with Trypanosoma theileri infection
Authors: Bittner Lilli , Krämer Kjelt , Wöckel Adriana , Snedec Teja , Delling Cora , Böttcher Denny , Köller Gabor , Baumgartner Walter , Richardt Wolfram , Starke Alexander
Published: January 2021

Background

Recumbent cows are a diagnostic challenge because of a wide range of differential diagnoses, which include trauma, neurological and metabolic disorders, malnutrition and mineral deficiencies. This case report describes recumbent suckler cows that presented as a herd problem. In addition to weakness due to inanition, Cu and Se deficiencies were considered as possible aetiologies of the recumbency. Furthermore, Trypanosoma (T.) theileri, a blood parasite of unknown importance in Germany, was detected in the blood of some cows.

Case presentation

Three recumbent cows were referred to the Clinic for Ruminants and Swine, Faculty of Veterinary Medicine of the University of Leipzig. They were unable to rise and had low body condition scores and rough hair coats. Haematological and serum biochemical analyses showed neutrophilia, electrolyte imbalances, increased activities of muscle and liver enzymes and decreased concentrations of trace elements, especially Copper (Cu) and Selenium (Se). T. theileri was detected in a routine blood smear from one cow. The cows did not respond to an intensive care protocol, which included intravenous fluids and electrolytes, mineral substitution, non-steroidal anti-inflammatories and antibiotics, and were therefore euthanized or died. Postmortem examination showed cachexia, subcutaneous and scleral oedema and muscular dystrophy, especially in the hind limbs. Follow-up examination of the herd of origin produced similar findings including the detection of T. theileri in a large proportion of the herd. Ration analysis revealed considerable undersupply of several nutrients.

Conclusions

Based on all findings, an aetiological diagnosis of trace mineral and nutrient deficiency with possible involvement of T. theileri was made.
Regulation of behavioral response to stress by microRNA-690
Authors: Park Jungyoung , Lee Joonhee , Choi Koeul , Kang Hyo Jung
Published: January 2021

Psychiatric disorders are affected by genetic susceptibility and environmental adversities. Therefore, the regulation of gene expression under certain environments, such as stress, is a key issue in psychiatric disorders. MicroRNAs (miRNAs) have been implicated as post-transcriptional regulators of several biological processes, which can be differentially controlled through the targeting of multiple mRNAs. However, studies reporting the functions of miRNAs in relation to stress are lacking. In this study, we identified a significant increase in the expression of miRNA-690 (miR-690) in the medial prefrontal cortex (mPFC) of FK506-binding protein 51 knock-out (Fkbp5 KO) mice. In addition, the expression pattern of miR-690 was similar to the sucrose preference of the same group in WT and Fkbp5 KO mice. miR-690 was injected into the mPFC using a recombinant adeno-associated virus mediated gene delivery method. After recovery, miR-690 overexpressing mice were exposed to restraint stress for 2 weeks. In the sucrose preference test and forced swim test, the stressed miR-690 overexpressing mice showed higher sucrose preference and lower immobility time, respectively, than stressed mice injected with the control virus. In the novel object recognition test, the stressed miR-690 overexpressing mice interacted longer with the novel object than those injected with the control virus. These results showed that miR-690 might play a role in stress resilience and could provide new insights into the epigenetic regulation of stress-associated biological functions and diseases, such as depression and post-traumatic stress disorder.
Linc-SCRG1 accelerates progression of hepatocellular carcinoma as a ceRNA of miR26a to derepress SKP2
Authors: Hu Jun-Jie , Zhou Cui , Luo Xin , Luo Sheng-Zheng , Li Zheng-Hong , Xu Zi-Xin , Xu Ming-Yi
Published: January 2021

Background

Increasing evidence has demonstrated that long noncoding RNAs (lncRNAs) have regulatory functions in hepatocellular carcinoma (HCC). The link between lincSCRG1 and HCC remains unclear.

Methods

To explore the lincSCRG1 regulation axis, bioinformatics, RIP and luciferase reporter assay were performed. The expressions of lincSCRG1-miR26a-SKP2 were detected in HCC tissues and cell lines through qPCR and western blot. The functions of HCC cells were investigated through in vitro assays (MTT, colony formation, transwell and flow cytometry) and the inner effect of lincSCRG1-miR26a in vivo was evaluated by xenografts and liver metatstatic nude mice models.

Results

LincSCRG1 was found to be strongly elevated in human HCC tissues and cell lines. MiR26a and S phase kinase-related protein 2 (SKP2) were predicted as the target miRNA for lincSCRG1 and the target gene for miR26a with direct binding sites, respectively. LincSCRG1 was verified as a competing endogenous RNA (ceRNA) via negative regulation of miR26a and derepression of SKP2 in HCC cells. Both overexpression of lincSCRG1 (ov-lincSCRG1) and inhibition of miR26a (in-miR26a) obviously stimulated cellular viability, colony formation, migration and proliferation of S phase cells and also significantly increased the protein levels of cyclinD1, CDK4, MMP2/3/9, Vimentin, and N-cadherin or inhibited the protein level of E-cadherin of HCC cells, while knockdown of lincSCRG1 (sh-lincSCRG1) and upregulation of miR26a (mi-miR26a) had the opposite effects on HCC cells. Cotransfection of in-miR26a or overexpression of SKP2 (ov-SKP2) with sh-lincSCRG1 could rescue the anticancer functions of sh-lincSCRG1, including suppressing proliferation and migration of HCC cells. Additionally, sh-lincSCRG1 could effectively inhibit the growth of subcutaneous xenograft tumours and lung metastasis, while the anticancer effect of sh-lincSCRG1 could be reversed by cotransfection of in-miR26a.

Conclusions

LincSCRG1 acts as a ceRNA of miR26a to restrict its ability to derepress SKP2, thereby inducing the proliferation and migration of HCC cells in vitro and in vivo. Depletion of lincSCRG1 could be used as a potential therapeutic approach in HCC.
Calculating the dose of cisplatin that is actually utilized in hyperthermic intraperitoneal chemotherapy among ovarian cancer patients
Authors: Wang Wu-yun , Wu Miao-fang , Wu Dong-bing , Wang Li-juan , Li Hui , Lin Zhong-qiu , Li Jing
Published: January 2021

Background

Hyperthermic intraperitoneal chemotherapy (HIPEC) is an important treatment for ovarian cancer. A certain portion of cisplatin exits the body via the perfusate at the end of HIPEC, so full-dose utilization cannot be achieved. Herein, we sought to explore how much cisplatin is actually utilized and its prognostic influence.

Methods

Cisplatin (70 mg/m2) was given at 43 °C for 90 min. The actually utilized dose (AD) of cisplatin was calculated using the following formula: AD (mg) = total dose (TD) (mg)-losing dose (LD) (mg); LD = volume (ml) of the perfusate (VPretained) that was retained in the HIPEC treatment system at the end of HIPEC * concentration of cisplatin in the perfusate (mg/ml).

Result

Sixty-two ovarian cancer patients were included. The median TD, median LD and median AD were 95 mg, 20.7 mg and 75.8 mg, respectively. The utility rate of cisplatin (AD/TD ratio) was 79.2%. On simple linear regression analysis, the TD and VPretained were found to significantly predict the AD. Based on these two factors, multiple linear regression analysis was conducted, and a significant regression equation was formulated [F (2, 59) = 71.419, P < 0.0001]: predicted AD (mg) = 30.079 + 0.667 TD (mg) – 0.010 VPretained (ml) (adjusted R2 = 0.698). In Cox regression analysis, AD was not noted to be associated with progression free survival or overall survival.

Conclusion

For ovarian cancer patients who receive cisplatin for HIPEC at 43 °C, the AD of cisplatin can be predicted using a regression equation and it has no prognostic impact.
Rate of rebound in follicle growth after cessation of ovarian stimulation in initial non‐responders: a prospective cohort study
Authors: Gleicher Norbert , Weghofer Andrea , Darmon Sarah K. , Barad David H.
Published: January 2021

Previously anecdotally observed rebounds in follicle growth after interruption of exogenous gonadotropins in absolute non-responders were the impetus for here reported study. In a prospective cohort study, we investigated 49 consecutive patients, absolutely unresponsive to maximal exogenous gonadotropin stimulation, for a so-called rebound response to ovarian stimulation. A rebound response was defined as follicle growth following complete withdrawal of exogenous gonadotropin stimulation after complete failure to respond to maximal gonadotropin stimulation over up to 5–7 days. Median age of study patients was 40.5 ± 5.1 years (range 23–52). Women with and without rebound did not differ significantly (40.0 ± 6.0 vs. 41.0 ± 7.0 years, P = 0.41), with 24 (49.0%) recording a rebound and 25 (51.0%) not. Among the former, 21 (87.5%) reached retrieval of 1–3 oocytes and 15 (30.6%) reached embryo transfer. A successful rebound in almost half of prior non-responders was an unsuspected response rate, as was retrieval of 1–3 oocytes in over half of rebounding patients. Attempting rebounds may, thus, represent another incremental step in very poor prognosis patients before giving up on utilization of autologous oocytes. Here presented findings support further investigations into the underlying physiology leading to such an unexpectedly high rebound rate.