bluuebunny/crossref_metadata_2025_split huggingface dataset:
Graphene oxide (GO)-based nanosheets with combined chemo/photothermal/photodynamic therapy to overcome gastric cancer (GC) paclitaxel resistance by reducing mitochondria-derived adenosine-triphosphate (ATP)
Authors: Guo Weihong , Chen Zhian , Feng Xiaoli , Shen Guodong , Huang Huilin , Liang Yanrui , Zhao Bingxia , Li Guoxin , Hu Yanfeng 
Published: May 2021

Abstract
Background
Paclitaxel (PTX) has been suggested to be a promising front-line drug for gastric cancer (GC), while P-glycoprotein (P-gp) could lead to drug resistance by pumping PTX out of GC cells. Consequently, it might be a hopeful way to combat drug resistance by inhibiting the out-pumping function of P-gp.

Results
In this study, we developed a drug delivery system incorporating PTX onto polyethylene glycol (PEG)-modified and oxidized sodium alginate (OSA)-functionalized graphene oxide (GO) nanosheets (NSs), called PTX@GO-PEG-OSA. Owing to pH/thermal-sensitive drug release properties, PTX@GO-PEG-OSA could induced more obvious antitumor effects on GC, compared to free PTX. With near infrared (NIR)-irradiation, PTX@GO-PEG-OSA could generate excessive reactive oxygen species (ROS), attack mitochondrial respiratory chain complex enzyme, reduce adenosine-triphosphate (ATP) supplement for P-gp, and effectively inhibit P-gp’s efflux pump function. Since that, PTX@GO-PEG-OSA achieved better therapeutic effect on PTX-resistant GC without evident toxicity.

Conclusions
In conclusion, PTX@GO-PEG-OSA could serve as a desirable strategy to reverse PTX’s resistance, combined with chemo/photothermal/photodynamic therapy.

Graphic Abstract
Chitosan oligosaccharide decorated liposomes combined with TH302 for photodynamic therapy in triple negative breast cancer
Authors: Ding Yinan , Yang Rui , Yu Weiping , Hu Chunmei , Zhang Zhiyuan , Liu Dongfang , An Yanli , Wang Xihui , He Chen , Liu Peidang , Tang Qiusha , Chen Daozhen 
Published: May 2021

Abstract
Background
Triple negative breast cancer (TNBC) is an aggressive tumor with extremely high mortality that results from its lack of effective therapeutic targets. As an adhesion molecule related to tumorigenesis and tumor metastasis, cluster of differentiation-44 (also known as CD44) is overexpressed in TNBC. Moreover, CD44 can be effectively targeted by a specific hyaluronic acid analog, namely, chitosan oligosaccharide (CO). In this study, a CO-coated liposome was designed, with Photochlor (HPPH) as the 660 nm light mediated photosensitizer and evofosfamide (also known as TH302) as the hypoxia-activated prodrug. The obtained liposomes can help diagnose TNBC by fluorescence imaging and produce antitumor therapy by synergetic photodynamic therapy (PDT) and chemotherapy.

Results
Compared with the nontargeted liposomes, the targeted liposomes exhibited good biocompatibility and targeting capability in vitro; in vivo, the targeted liposomes exhibited much better fluorescence imaging capability. Additionally, liposomes loaded with HPPH and TH302 showed significantly better antitumor effects than the other monotherapy groups both in vitro and in vivo.

Conclusion
The impressive synergistic antitumor effects, together with the superior fluorescence imaging capability, good biocompatibility and minor side effects confers the liposomes with potential for future translational research in the diagnosis and CD44-overexpressing cancer therapy, especially TNBC.

Graphic abstract
Predictors for quality of life improvement after surgery for degenerative cervical myelopathy: a prospective multi-center study
Authors: Inose Hiroyuki , Hirai Takashi , Yoshii Toshitaka , Kimura Atsushi , Takeshita Katsushi , Inoue Hirokazu , Maekawa Asato , Endo Kenji , Miyamoto Takuya , Furuya Takeo , Nakamura Akira , Mori Kanji , Kanbara Shunsuke , Imagama Shiro , Seki Shoji , Matsunaga Shunji , Okawa Atsushi 
Published: May 2021

Abstract
Background
Degenerative cervical myelopathy (DCM) can significantly impair a patient’s quality of life (QOL). In this study, we aimed to identify predictors associated with QOL improvement after surgery for DCM.

Methods
This study included 148 patients who underwent surgery for DCM. The European QOL-5 Dimension (EQ-5D) score, the Japanese Orthopedic Association for the assessment of cervical myelopathy (C-JOA) score, and the Nurick grade were used as outcome measures. Radiographic examinations were performed at enrollment. The associations of baseline variables with changes in EQ-5D scores from preoperative to 1-year postoperative assessment were investigated using a multivariable linear regression model.

Results
The EQ-5D and C-JOA scores and the Nurick grade improved after surgery (P < 0.001, P < 0.001, and P < 0.001, respectively). Univariable analysis revealed that preoperative EQ-5D and C-JOA scores were significantly associated with increased EQ-5D scores from preoperative assessment to 1 year after surgery (P < 0.0001 and P = 0.045). Multivariable regression analysis showed that the independent preoperative predictors of change in QOL were lumbar lordosis (LL), sacral slope (SS), and T1 pelvic angle (TPA). According to the prediction model, the increased EQ-5D score from preoperatively to 1 year after surgery = 0.308 − 0.493 × EQ-5D + 0.006 × LL − 0.008 × SS + 0.004 × TPA.

Conclusions
Preoperative LL, SS, and TPA significantly impacted the QOL of patients who underwent surgery for DCM. Less improvement in QOL after surgery was achieved in patients with smaller LL and TPA and larger SS values. Patients with these risk factors may therefore require additional support to experience adequate improvement in QOL.
Attracting and retaining physicians in less attractive specialties: the role of continuing medical education
Authors: Thi Nguyen Van Anh , Könings Karen D. , Scherpbier Albert J. J. A. , van Merriënboer Jeroen J. G. 
Published: May 2021

Abstract
Background
Less attractive specialties in medicine are struggling to recruit and retain physicians. When properly organized and delivered, continuing medical education (CME) activities that include short courses, coaching in the workplace, and communities of practice might offer a solution to this problem. This position paper discusses how educationalists can create CME activities based on the self-determination theory that increase physicians’ intrinsic motivation to work in these specialties.

Main content
The authors propose a set of guidelines for the design of CME activities that offer physicians meaningful training experiences within the limits of the available resources and support. First, to increase physicians’ sense of professional relatedness, educationalists must conduct a learner needs assessment, evaluate CME’s long-term outcomes in work-based settings, create social learning networks, and involve stakeholders in every step of the CME design and implementation process. Moreover, providing accessible, practical training formats and giving informative performance feedback that authentically connects to learners' working life situation increases physicians’ competence and autonomy, so that they can confidently and independently manage the situations in their practice contexts. For each guideline, application methods and instruments are proposed, making use of relevant literature and connecting to the self-determination theory.

Conclusions
By reducing feelings of professional isolation and reinforcing feelings of competence and autonomy in physicians, CME activities show promise as a strategy to recruit and retain physicians in less attractive specialties.
Ethylmalonic encephalopathy and liver transplantation: long-term outcome of the first treated patient
Authors: Olivieri Giorgia , Martinelli Diego , Longo Daniela , Grimaldi Chiara , Liccardo Daniela , Di Meo Ivano , Pietrobattista Andrea , Sidorina Anna , Semeraro Michela , Dionisi-Vici Carlo 
Published: May 2021

Abstract
Background
Ethylmalonic encephalopathy (EE) is a severe intoxication-type metabolic disorder with multisystem clinical features and leading to early death. In 2014, based on the promising results obtained by liver-targeted gene therapy in Ethe1−/− mouse model, we successfully attempted liver transplantation in a 9-month-old EE girl. Here we report her long-term follow-up, lasting over 6 years, with a comprehensive evaluation of clinical, instrumental and biochemical assessments.

Results
Neurological signs initially reverted, with a clinical stabilization during the entire follow-up course. Accordingly, gross motor functions improved and then stabilized. Psychomotor evaluations documented an increasing communicative intent, the acquisition of new social skills and the capability to carry out simple orders. Neurophysiological assessments, which included EEG, VEP/ERG and BAEPs, remained unchanged. Brain MRI also stabilized, showing no further lesions and cerebral atrophy improvement. Compared to pre-transplant assessments, urinary ethylmalonic acid strikingly reduced, and plasma thiosulphate fully normalized. The child maintained good clinical conditions and never experienced metabolic crises nor epileptic seizures.

Conclusions
The long-term follow-up of the first EE transplanted patient demonstrates that liver transplantation stabilizes, or even improves, disease course, therefore representing a potentially elective option especially in early-diagnosed patients, such as those detected by newborn screening, before irreversible neurological damage occurs.
Super-enhancers: a new frontier for epigenetic modifiers in cancer chemoresistance
Authors: Li Guo-Hua , Qu Qiang , Qi Ting-Ting , Teng Xin-Qi , Zhu Hai-Hong , Wang Jiao-Jiao , Lu Qiong , Qu Jian 
Published: May 2021

AbstractAlthough new developments of surgery, chemotherapy, radiotherapy, and immunotherapy treatments for cancer have improved patient survival, the emergence of chemoresistance in cancer has significant impacts on treatment effects. The development of chemoresistance involves several polygenic, progressive mechanisms at the molecular and cellular levels, as well as both genetic and epigenetic heterogeneities. Chemotherapeutics induce epigenetic reprogramming in cancer cells, converting a transient transcriptional state into a stably resistant one. Super-enhancers (SEs) are central to the maintenance of identity of cancer cells and promote SE-driven-oncogenic transcriptions to which cancer cells become highly addicted. This dependence on SE-driven transcription to maintain chemoresistance offers an Achilles’ heel for chemoresistance. Indeed, the inhibition of SE components dampens oncogenic transcription and inhibits tumor growth to ultimately achieve combined sensitization and reverse the effects of drug resistance. No reviews have been published on SE-related mechanisms in the cancer chemoresistance. In this review, we investigated the structure, function, and regulation of chemoresistance-related SEs and their contributions to the chemotherapy via regulation of the formation of cancer stem cells, cellular plasticity, the microenvironment, genes associated with chemoresistance, noncoding RNAs, and tumor immunity. The discovery of these mechanisms may aid in the development of new drugs to improve the sensitivity and specificity of cancer cells to chemotherapy drugs.
Different limb lengths in gastric bypass surgery: study protocol for a Swiss multicenter randomized controlled trial (SLIM)
Authors: Kraljević Marko , Schneider Romano , Wölnerhanssen Bettina , Bueter Marco , Delko Tarik , Peterli Ralph 
Published: May 2021

Abstract
Background
Obesity and type 2 diabetes mellitus are reaching epidemic proportions. In morbidly obese patients, bariatric operations lead to sustained weight loss and relief of comorbidities in the majority of patients. Laparoscopic Roux-Y-gastric bypass (RYGB) is one of the most frequently performed operations, but it is still unknown why some patients respond better than others. Therefore, a number of variations of this operation have been introduced. Recent evidence suggests that a longer bypassed biliopancreatic limb (BPL) has the potential to be more effective compared to the standard RYGB with a shorter BPL length. This article describes the design and protocol of a randomized controlled trial comparing the outcome of a RYGB operation with a long versus short BPL.

Methods/design
The trial is designed as a multicenter, randomized, patient- and observer-blinded trial. The relevant ethics committee has approved the trial protocol. To demonstrate that long BPL RYGB is superior compared to short BPL RYGB in terms of weight loss and resolution of T2DM, the study is conducted as a superiority trial. Postoperative percent total weight loss and nutritional deficiency rate are the primary endpoints, whereas morbidity, mortality, remission of obesity-related comorbidities and quality of life are secondary endpoints. Eight hundred patients, between 18 and 65 years and with a body mass index (BMI) from 35 to 60 kg/m2 who meet the regulatory rules for bariatric surgery in Switzerland, will be randomized. The endpoints and baseline measurements will be assessed pre-, intra-, and postoperatively.

Discussion
With its high number of patients and a 5-year follow-up, this study will answer questions about effectiveness and safety of long BPL RYGB and provide level I evidence for improvement of the standard RYGB. These findings might therefore potentially influence global bariatric surgery guidelines.

Trial registration
ClinicalTrials.gov NCT04219787. Registered on 7 January 2020.
Assessment of the efficacy and safety of tocilizumab in patients over 80 years old with giant cell arteritis
Authors:   for the French Study Group for Large Vessel Vasculitis (GEFA), de Boysson Hubert , Le Besnerais Maelle , Blaison Félix , Daumas Aurélie , Jarrot Pierre-André , Perrin François , Tieulié Nathalie , Maria Alexandre , Duffau Pierre , Gombert Bruno , Samson Maxime , Espitia Olivier , Lambert Marc , Mékinian Arsène , Aouba Achille 
Published: May 2021

Abstract
Objective
To assess the efficacy and tolerance of tocilizumab (TCZ) in giant cell arteritis (GCA) patients over 80.

Method
GCA patients over 80 years old from the French Study Group for Large Vessel Vasculitis register who received TCZ were analyzed.

Results
Twenty-one GCA patients (median age 84 [81–90] years old, including nine over 85) received TCZ for the following nonexclusive reasons: glucocorticoid (GC)-sparing effect in 14, relapsing disease in 8, disease severity in 4, and/or failure of another immunosuppressant in 4. TCZ was introduced with GCs at diagnosis in 6 patients and at 8 [3–37] months after GC initiation in 15 others. After a median delay of 8 [2–21] months post-TCZ introduction, 14 (67%) patients were able to definitively stop GCs, including 6 who were GC-dependent before TCZ. At the last follow-up (median 20 [3–48] months), 11 (52%) patients had definitively stopped TCZ, and 2 additional patients had stopped but relapsed and resumed TCZ.
Seven (33%) patients experienced 11 adverse events: hypercholesterolemia in 4 patients; infections, i.e., pyelonephritis, bronchitis, and fatal septic shock associated with mesenteric infarction following planned surgery (GCs were stopped for 1 year and TCZ infusions for 2 months), respectively, in 3 patients; moderate thrombocytopenia and moderate neutropenia in 2 patients; and a 5-fold increase in transaminase levels in another that improved after TCZ dose reduction.

Conclusion
TCZ remains a valuable GC-sparing option in the oldest GCA patients with an interesting risk-benefit ratio. Mild-to-moderate adverse events were observed in one-third of patients.
Association of vitamin D-binding protein and vitamin D3 with insulin and homeostatic model assessment (HOMA-IR) in overweight and obese females
Authors: Setayesh Leila , Casazza Krista , Moradi Nariman , Mehranfar Sanaz , Yarizadeh Habib , Amini Abbas , Yekaninejad Mir Saeed , Mirzaei Khadijeh 
Published: May 2021

Abstract
Objective
Equivocal association the contribution of 25-hydroxyvitamin D (25(OH)D) and the well-accepted role of vitamin D-binding protein (VDBP) on bioavailability of 25(OH)D or its independent roles, has led to possible association of the VDBP in glucose metabolism. This study was conducted to evaluate the relationships among 25(OH)D, VDBP, glucose/insulin metabolism and homeostatic model assessment (HOMA-IR). Blood samples were collected from 236 obese and overweight women. VDBP and 25(OH)D levels, and biochemical parameters were measured using an enzyme-linked immunosorbent assay (ELISA). An impedance fat analyzer was utilized to acquire the body composition.

Results
Using the multivariate linear regression, a reverse relationship was observed between VDBP and (HOMA-IR), such that women with higher VDBP displayed lower insulin resistance. The relationship was independent of age, body mass index, standardized energy intake and physical activity (p = 0.00). No significant relationship between 25(OH)D levels, FBS, body composition or insulin resistance were observed (p > 0.2). Current study observed that higher level of VDBP may be associated with lower levels of insulin and HOMA-IR, thus the evaluation of VDBP in diverse population groups seems to have significant clinical value in evaluating the prevalence of DM or early stage of glucose intolerance.
Association between water and sanitation and soil-transmitted helminthiases: Analysis of the Brazilian National Survey of Prevalence (2011–2015)
Authors: Mingoti Poague Kasandra Isabella Helouise , Mingoti Sueli Aparecida , Heller Léo 
Published: May 2021

Abstract
Background
Most of the studies conducted in Brazil assessing the relationship between water, sanitation and hygiene (WASH) and Soil-transmitted helminth (STH) infections, have focused on cases, reflecting the reality of small areas and not of a countrywide situation. In order to fill this gap, the current paper presents an epidemiological study exploring the association between water and sanitation and STHs prevalence in students from 7 to 17 years old, in all 27 Brazilian Federation Units.

Methods
Three ecological studies were carried out considering the prevalence of ascariasis, trichuriasis, and hookworm as outcome variables. The sample consisted of 197,567 students aged 7–17 years old living in 521 Brazilian municipalities. Data were retrieved from the National Survey on the Prevalence of Schistosomiasis mansoni and Soil-transmitted helminth infections (2011–2015). The Generalized Linear Model with the negative binomial distribution was used to evaluate the statistical association between outcomes and explanatory variables. Univariate and Multivariate analyses were conducted with 25 and 5 % significance levels, respectively. Data were aggregated considering municipalities as the geographical unit for analysis.

Results
Protective association was found between access to filtered water and adequate sanitation in schools with ascariasis (RR 0.989, CI 95 % 0.983–0.996; RR 0.988, CI 95 % 0.977–0.998), access to filtered water in schools with trichuriasis (RR 0.986, CI 95 % 0.979–0.993) and adequate sanitation at home with hookworm ((RR 0.989, CI 95 % 0.982–0.996). The percentage of population served with Bolsa Família Program, used as a proxy for poverty, was the only significant variable common to all models.

Conclusions
Our findings support that WASH, both in schools and homes, are essential to schoolchildren health with regard to STHs. However, sanitary interventions will not be fully effective in preventing STH infections without promoting access to quality public services, particularly for people living in poverty, the most vulnerable group.
Association of breastfeeding and risk of metabolic syndrome and its components in postmenopausal parous women: Korea national health and nutrition examination survey (2010 ~ 2016)
Authors: Lee Jusuk , Kim Taehong 
Published: May 2021

Abstract
Background
Understanding the relationship between breastfeeding (BF) and metabolic syndrome (Mets) is important for maternal long-term health benefits and disease prevention. This study aimed to examine the association between BF and Mets and its components among postmenopausal parous Korean women.

Methods
This cross-sectional study on 10,356 Korean women used nationally representative data from the KNHANES from 2010 to 2016. Anthropometric, laboratory data and manual BP were measured. A multivariate logistic regression analysis was conducted to examine the association of BF with Mets and its components after adjusting for potential confounding variables. A p-value < 0.05 was to be considered statistically significant.

Results
Mets was present in 42% of the study participants. The BF group had low household income and education level. The prevalence of Mets in the BF group was higher than that in the non-BF group (42.69% vs. 34.76%, p <  0.001). BF was associated with increased risk of Mets (odds ratio [OR]: 1.4, 95% confidence interval [CI]: 1.18–1.65, p <  0.001). The BF group was at higher risks for diabetes (OR: 1.5, 95%CI: 1.14–1.98), hypertension (OR: 1.32, 95%CI: 1.03–1.68), hypertriglyceridemia (OR: 1.42, 95%CI: 1.02–1.99) and low high-density lipoprotein cholesterol (OR: 1.32, 95%CI: 1.06–1.65).

Conclusion
In this study, BF did not affect decreasing the prevalence of Mets and its components.
Access of Patients With Lung Cancer to High Technology Radiation Therapy in Brazil
Authors: Faroni Lilian Dantonino , Rosa Arthur Accioly , Aran Veronica , Ramos Renan Serrano , Ferreira Carlos Gil 
Published: May 2021

PURPOSE Lung cancer is a global health problem, with more than 220,000 new cases and 150,000 deaths per year in the United States. Likewise, in Brazil, lung cancer is the most lethal cancer with 30,200 new cases expected in 2020. Regarding treatment types, radiation therapy (RT) represents an important approach, since 60%-70% of the patients will receive this modality of treatment during the course of their disease. However, access to RT remains challenging because of the socioeconomic inequalities in the Brazilian population, where approximately 100,000 patients/year die without access to RT. This work provides an overview on the availability of high technology RT in Brazil. METHODS A retrospective study was performed using the Brazilian Radiotherapy Census, local public and private databases, and the current literature published in 2019. RESULTS The Brazilian radiotherapy network relies on approximately 363 linear accelerators and 20 cobalt machines that remain operational. Most of these machines are installed at public health facilities. Regarding high technology, intensity-modulated RT is available in 53.7% (n = 130) and volumetric modulated arc therapy in 28.5% (n = 69) of the institutions, although only 19.8% (n = 48) of those facilities are capable of performing image-guided RT using cone beam computed tomography. Considering only the public health care system, the scenario is more restricted, with 40.1% (n = 65) of the institutions offering intensity-modulated RT, 21% (n = 34) volumetric modulated arc therapy, and 14.8% (n = 24) using cone beam computed tomography. Because of these scare resources, only 16% of Radiation Departments offer stereotactic body RT. CONCLUSION Brazil still needs to improve and provide high and safer RT technologies to patients with lung cancer across all Brazilian regions to attend the population needs and obtain better patient outcomes.