bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

AbstractBackgroundThere 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.MethodsA 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.ResultsThe 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).ConclusionART 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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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.