bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nanoengineering a metal–organic framework for osteosarcoma chemo-immunotherapy by modulating indoleamine-2,3-dioxygenase and myeloid-derived suppressor cells
Authors: Fan Qingxin , Zuo Jing , Tian Hailong , Huang Canhua , Nice Edouard C. , Shi Zheng , Kong Qingquan 
Published: May 2022

Abstract
Background
The high postoperative recurrence rate and refractoriness of relapsed tumors are still a conundrum for the clinical management of osteosarcoma (OS). New therapeutic options are urgently needed. Depriving the nourishment of myeloid-derived suppressor cells is a novel strategy to improve the immunosuppressive tumor microenvironment for enhanced OS therapy.

Methods
We synthesized a hyaluronic acid (HA)-modified metal–organic framework for combinational chemotherapy and immunotherapy of OS. Zeolitic Imidazolate Framework-8 (ZIF-8) was prepared by a one-pot synthetic method, Gemcitabine (Gem) and D-1-Methyltryptophan (D-1-MT) were loaded into the ZIF-8 during the synthesis process to make ZIF-8@Gem/D-1-MT nanoparticles (NPs). The end product (HA/ZIF-8@Gem/D-1-MT NPs) was obtained by HA modification on the surface of ZIF-8@Gem/D-1-MT NPs. The obtained HA/ZIF-8@Gem/D-1-MT NPs have excellent potential as a drug delivery vector for chemotherapy and immunotherapy in vitro and vivo.

Results
The results indicate that HA/ZIF-8@Gem/D-1-MT NPs were readily taken up by OS cells, and that the Gem and D-1-MT were effectively released into the acidic environment. The HA/ZIF-8@Gem/D-1-MT NPs could efficiently decrease OS cell viability (proliferation, apoptosis, cell cycle, migration and invasion). And HA/ZIF-8@Gem/D-1-MT NPs could reactivate antitumor immunity by inhibiting indoleamine 2,3 dioxygenase and myeloid-derived suppressor cells. Furthermore, animal experiments confirmed that HA/ZIF-8@Gem/D-1-MT NPs could induce intratumoral immune responses and inhibit tumor growth. Additionally, HA/ZIF-8@Gem/D-1-MT NPs have a good safety profile.

Conclusions
Our findings demonstrate that the combination of Gem with D-1-MT brings new hope for the improved treatment of OS, while the generation of the nanosystem has increased the application potential and flexibility of this strategy.
“Multidisciplinary management of post- infective osteoarthritis and secondary condylar resorption of temporomandibular joint: a case report in a 9 years-old female patient and a review of literature”
Authors: Festa Paola , Arezzo Elena , Vallogini Giulia , Vittucci Anna Chiara , Barbuti Domenico , Galeotti Angela 
Published: May 2022

Abstract
Background
Osteoarthritis and condylar resorption of temporomandibular joint (TMJ) has rarely been reported in children as consequence of otologic disease. We describe the management of a case in a 9-year-old female as long-term complication of an otomastoiditis and review the literature currently available on this topic.

Case presentation
A nine-years-old female patient referred to Emergency Room of Bambino Gesù Children’s Research Hospital, IRCCS (Rome,Italy) for an acute pain in the left preauricular area and reduced mandibular movements. In the medical history an otomastoiditis and periorbital cellulitis was reported at the age of six with complete remission of symptoms after antibiotic treatment. No recent history of facial trauma and no previous orthodontic treatment were reported. She was referred to a pediatric dentist that conducted a clinical examination according to the Diagnostic Criteria of Temporomandibular Disorders (DC/TMD) and was diagnosed with bilateral myalgia of the masticatory muscles and arthralgia at the level of the left TMJ. Then, a complete diagnostic path was performed that included multidisciplinary examinations by a rheumatologist, infectious disease specialist, ear nose and throat (ENT) doctor, a maxillofacial surgeon and a medical imaging specialist. Differential diagnosis included juvenile idiopathic arthritis, idiopathic condylar resorption, trauma, degenerative joint disease, neurological disease. Finally, unilateral post-infective osteoarthritis of the left TMJ with resorption of mandibular condyle was diagnosed. The patient went through a pharmacological therapy with paracetamol associated to counselling, jaw exercises and occlusal bite plate. After 1 month, the patient showed significant reduction of orofacial pain and functional recovery that was confirmed also one-year post-treatment. The novelty of this clinical case lies in the accurate description of the multidisciplinary approach with clinical examination, the differential diagnosis process and the management of TMD with conservative treatment in a growing patient.

Conclusions
Septic arthritis of temporomandibular joint and condylar resorption were described as complications of acute otitis media and/or otomastoiditis in children. We evidenced the importance of long-term follow-up in children with acute media otitis or otomastoiditis due to the onset of TMJ diseases. Furthermore, in the multidisciplinary management of orofacial pain the role of pediatric dentist is crucial for the diagnostic and therapeutic pathway to avoid serious impairment of mandibular function.
A behavior change wheel-based interactive pictorial health education program for hypertensive patients with low blood pressure health literacy: study protocol for a randomized controlled trial
Authors: Gan Wei , Zhang Qinghua , Yang Dan , Yin Jinyu , Wang Yujie , Song Li , Chen Ting , Qi Huan 
Published: May 2022

Abstract
Background
The prevalence of hypertension is increasing worldwide. Hypertension self-management usually involves the application and consideration of oral, written, or quantitative information. Hypertensive patients in China have limited high blood pressure health literacy (HBP-HL), which may lead to poorer clinical outcomes. This study aims to determine the feasibility and effectiveness of an interactive pictorial health education program based on behavior change wheel (BCW) theory and its effect on HBP-HL, self-efficacy, self-management ability, and health-related quality of life (HRQOL) in hypertensive patients with low HBP-HL.

Methods
This study is a randomized controlled trial (RCT). One of the municipal districts in Huzhou, China, will be randomly selected, and two communities with similar conditions within this district will be screened and selected. A total of 120 hypertensive patients aged 18 years and older will be recruited from these two community settings. One of the communities will be randomly allocated to an interactive pictorial health education program conducted by a comprehensive health literacy strategy that includes (i) training participants in effective health communication skills that address issues encountered in seeking medical care and (ii) the use of self-developed interactive pictorial hypertension education to improve patient understanding and behaviors versus a control group (routine community lecture health education only). The primary outcome measure is HBP-HL. Secondary outcomes are self-efficacy, self-management ability, HRQOL, social support, and improvement in blood pressure. Outcomes will be collected at 6, 9, and 12 months from trial entry.

Discussion
The strengths of this study are the establishment of a new health management program for hypertensive patients that closely combines BCW theory and health literacy. This trial has the potential to improve HBP-HL in hypertensive Chinese patients with low health literacy to improve the self-management of hypertension and help control blood pressure.

Trial registration
Clinical Trials.gov Protocol Registration and Results System ID NCT04327102. Prospectively registered on February 29, 2020
Community structure and insecticide resistance of malaria vectors in northern-central Myanmar
Authors: Zhong Daibin , Aung Pyae Linn , Mya Maung Maung , Wang Xiaoming , Qin Qian , Soe Myat Thu , Zhou Guofa , Kyaw Myat Phone , Sattabongkot Jetsumon , Cui Liwang , Yan Guiyun 
Published: May 2022

Abstract
Background
Myanmar is one of the six countries in the Greater Mekong Subregion (GMS) of Southeast Asia. Malaria vectors comprise many Anopheles species, which vary in abundance and importance in malaria transmission among different geographical locations in the GMS. Information about the species composition, abundance, and insecticide resistance status of vectorial systems in Myanmar is scarce, hindering our efforts to effectively control malaria vectors in this region.

Methods
During October and November 2019, larvae and adult females of Anopheles mosquitoes were collected in three sentinel villages of Banmauk township in northern Myanmar. Adult female mosquitoes collected by cow-baited tent collection (CBTC) and adults reared from field-collected larvae (RFCL) were used to determine mortality rates and knockdown resistance (kdr) against deltamethrin using the standard WHO susceptibility test. Molecular species identification was performed by multiplex PCR and ITS2 PCR, followed by DNA sequencing. The kdr mutation at position 1014 of the voltage-gated sodium channel gene was genotyped by DNA sequencing for all Anopheles species tested.

Results
A total of 1596 Anopheles mosquitoes from seven morphologically identified species groups were bioassayed. Confirmed resistance to deltamethrin was detected in the populations of An. barbirostris (s.l.), An. hyrcanus (s.l.), and An. vagus, while possible resistance was detected in An. annularis (s.l.), An. minimus, and An. tessellatus. Anopheles kochi was found susceptible to deltamethrin. Compared to adults collected by CBTC, female adults from RFCL had significantly lower mortality rates in the four species complexes. A total of 1638 individuals from 22 Anopheles species were molecularly identified, with the four most common species being An. dissidens (20.5%) of the Barbirostris group, An. peditaeniatus (19.4%) of the Hyrcanus group, An. aconitus (13.4%) of the Funestus group, and An. nivipes (11.5%) of the Annularis group. The kdr mutation L1014F was only detected in the homozygous state in two An. subpictus (s.l.) specimens and in a heterozygous state in one An. culicifacies (s.l.) specimen.

Conclusions
This study provides updated information about malaria vector species composition and insecticide resistance status in northern Myanmar. The confirmed deltamethrin resistance in multiple species groups constitutes a significant threat to malaria vector control. The lack or low frequency of target-site resistance mutations suggests that other mechanisms are involved in resistance. Continual monitoring of the insecticide resistance of malaria vectors is required for effective vector control and insecticide resistance management.

Graphical Abstract
Comparison of visceral fat lipolysis adaptation to high-intensity interval training in obesity-prone and obesity-resistant rats
Authors: Liu Yang , Li Yu , Cheng Baishuo , Feng Shige , Zhu Xiangui , Chen Wei , Zhang Haifeng 
Published: May 2022

AbstractBackground/objectivesVisceral obesity is one of the key features of metabolic syndrome. High-intensity interval training (HIIT) could effectively reduce visceral fat, but its effects show strong heterogeneity in populations with different degrees of obesity. The mechanism may be related to the differential adaptation to training between obesity phenotypes, namely obesity prone (OP) and obesity resistant (OR). The aim of the present study was to compare adaptive changes of visceral adipose lipolysis adaptation to HIIT between OP and OR animals and further explore the upstream pathway.MethodsOP and OR Sprague Dawley rats were established after feeding a high-fat diet for 6 weeks; they were then divided into HIIT (H-OP and H-OR) and control (C-OP and C-OR) groups. After 12 weeks of HIIT or a sedentary lifestyle, animals were fasted for 12 h and then sacrificed for histology as well as gene and protein analysis. Visceral adipocytes were isolated without fasting for catecholamine stimulation and β3-adrenergic receptor (β3-AR) blockade in vitro to evaluate the role of upstream pathways.ResultsAfter training, there were no differences in weight loss or food intake between OP and OR rats (P > 0.05). However, the visceral fat mass, adipocyte volume, serum triglycerides and liver lipids of OP rats decreased by more than those of OR rats (P < 0.05). Meanwhile, the cell lipolytic capacity and the increase in the expression of β3-AR were higher in the OP compared with OR groups (P < 0.05). Although training did not increase sympathetic nervous system activity (P > 0.05), the cell sensitivity to catecholamine increased significantly in the OP compared with OR groups (P < 0.05). Following blocking β3-AR, the increased sensitivity disappeared.ConclusionWith HIIT, OP rats lost more visceral fat than OR rats, which was related to stronger adaptive changes in lipolysis. Increased β3-AR expression mediated this adaptation.
Clinical and humanistic impact of pharmacotherapeutic follow-up in patients with type 1 diabetes mellitus treated judicially
Authors: Mendonça Thays S. , Oliveira William N. , Belo Vinícius S. , Silva Eduardo S. , Pereira Mariana L. , Obreli-Neto Paulo R. , Baldoni André O. 
Published: May 2022

Abstract
Background
There is a lack of studies that assess the effectiveness of pharmacotherapeutic follow-up in the context of the judicialization of insulin analogues.

Aims
To evaluate the clinical and humanistic impact of pharmacotherapeutic follow-up in patients with type 1 diabetes mellitus who receive insulin analogues by judicial decision in a Brazilian municipality.

Methods
A quasi-experimental study of the before-and-after type was carried out through pharmacotherapeutic follow-up. Patients who accepted to participate in the study underwent laboratory tests of glycemic and lipid profile before and after the intervention, and underwent five pharmaceutical consultations. In addition, quality of life and health, knowledge, and skills related to insulin application techniques were analyzed.

Results
28 patients participated in all stages. Of these, most were female (53.6%), with a mean age of 32.8 ± 11.6 years. After the intervention, there was a reduction in blood glucose levels, blood pressure, and increased body mass index. In addition, there was greater knowledge and skills regarding insulin application techniques, improved quality of life, health, greater number of medications used, reduction of pharmacotherapeutic problems, and improvement in eating habits.

Conclusion
The pharmacotherapeutic follow-up promoted clinical and humanistic benefits, with improvement in quality of life and health.
Efficacy and safety of umbilical cord-derived mesenchymal stem cells in Chinese adults with type 2 diabetes: a single-center, double-blinded, randomized, placebo-controlled phase II trial
Authors: Zang Li , Li Yijun , Hao Haojie , Liu Jiejie , Cheng Yu , Li Bing , Yin Yaqi , Zhang Qian , Gao Fei , Wang Haibin , Gu Shi , Li Jia , Lin Fengxiang , Zhu Yingfei , Tian Guanglei , Chen Yulong , Gu Weijun , Du Jin , Chen Kang , Guo Qinghua , Yang Guoqing , Pei Yu , Yan Wenhua , Wang Xianling , Meng Junhua , Zhang Saichun , Ba Jianming , Lyu Zhaohui , Dou Jingtao , Han Weidong , Mu Yiming 
Published: May 2022

Abstract
Background
To determine the efficacy and safety of umbilical cord-derived mesenchymal stem cells (UC-MSCs) in Chinese adults with type 2 diabetes mellitus (T2DM).

Methods
In this single-center, double-blinded, randomized, placebo-controlled phase II trial, 91 patients were randomly assigned to receive intravenous infusion of UC-MSCs (n = 45) or placebo (n = 46) three times with 4-week intervals and followed up for 48 weeks from October 2015 to December 2018. The primary endpoint was the percentage of patients with glycated hemoglobin (HbA1c) levels of < 7.0% and daily insulin reduction of ≥ 50% at 48 weeks. Additional endpoints were changes of metabolic control, islet β-cell function, insulin resistance, and safety.

Results
At 48 weeks, 20% of the patients in the UC-MSCs group and 4.55% in the placebo group reached the primary endpoint (p < 0.05, 95% confidence interval (CI) 2.25–28.66%). The percentage of insulin reduction of the UC-MSCs group was significantly higher than that of the placebo group (27.78% versus 15.62%, p < 0.05). The levels of HbA1c decreased 1.31% (9.02 ± 1.27% to 7.52 ± 1.07%, p < 0.01) in the UC-MSCs group, and only 0.63% in the placebo group (8.89 ± 1.11% to 8.19 ± 1.02%, p˃0.05; p = 0.0081 between both groups). The glucose infusion rate (GIR) increased significantly in the UC-MSCs group (from 3.12 to 4.76 mg/min/kg, p < 0.01), whereas no significant change was observed in the placebo group (from 3.26 to 3.60 mg/min/kg, p ˃ 0.05; p < 0.01 between both groups). There was no improvement in islet β-cell function in both groups. No major UC-MSCs transplantation-related adverse events occurred.

Conclusions
UC-MSCs transplantation could be a potential therapeutic approach for Chinese adults with T2DM.
Trial registration This study was registered on ClinicalTrials.gov (identifier: NCT02302599).
Exosomes and autophagy in ocular surface and retinal diseases: new insights into pathophysiology and treatment
Authors: Ma Shisi , Liu Xiao , Yin Jiayang , Hao Lili , Diao Yuyao , Zhong Jingxiang 
Published: May 2022

Abstract
Background
Ocular surface and retinal diseases are widespread problems that cannot be ignored in today’s society. However, existing prevention and treatment still have many shortcomings and limitations, and fail to effectively hinder the occurrence and development of them.

Main body
The purpose of this review is to give a detailed description of the potential mechanism of exosomes and autophagy. The eukaryotic endomembrane system refers to a range of membrane-bound organelles in the cytoplasm that are interconnected structurally and functionally, which regionalize and functionalize the cytoplasm to meet the needs of cells under different conditions. Exosomal biogenesis and autophagy are two important components of this system and are connected by lysosomal pathways. Exosomes are extracellular vesicles that contain multiple signaling molecules produced by multivesicular bodies derived from endosomes. Autophagy includes lysosome-dependent degradation and recycling pathways of cells or organelles. Recent studies have revealed that there is a common molecular mechanism between exosomes and autophagy, which have been, respectively, confirmed to involve in ocular surface and retinal diseases.

Conclusion
The relationship between exosomes and autophagy and is mostly focused on fundus diseases, while a deeper understanding of them will provide new directions for the pathological mechanism, diagnosis, and treatment of ocular surface and retinal diseases.
Sex differences in the aging murine urinary bladder and influence on the tumor immune microenvironment of a carcinogen-induced model of bladder cancer
Authors: Hamade Ali , Li Deyang , Tyryshkin Kathrin , Xu Minqi , Conseil Gwenaelle , Yolmo Priyanka , Hamilton Jake , Chenard Stephen , Robert Siemens D. , Koti Madhuri 
Published: May 2022

AbstractSex and age associated differences in the tumor immune microenvironment of non-muscle invasive bladder (NMIBC) cancer and associated clinical outcomes are emerging indicators of treatment outcomes. The incidence of urothelial carcinoma of the bladder is four times higher in males than females; however, females tend to present with a more aggressive disease, a poorer response to immunotherapy and suffer worse clinical outcomes. Recent findings have demonstrated sex differences in the tumor immune microenvironment of non-muscle invasive and muscle invasive bladder cancer and associated clinical outcomes. However, a significant gap in knowledge remains with respect to the current pre-clinical modeling approaches to more precisely recapitulate these differences towards improved therapeutic design. Given the similarities in mucosal immune physiology between humans and mice, we evaluated the sex and age-related immune alterations in healthy murine bladders. Bulk-RNA sequencing and multiplex immunofluorescence-based spatial immune profiling of healthy murine bladders from male and female mice of age groups spanning young to old showed a highly altered immune landscape that exhibited sex and age associated differences, particularly in the context of B cell mediated responses. Spatial profiling of healthy bladders, using markers specific to macrophages, T cells, B cells, activated dendritic cells, high endothelial venules, myeloid cells and the PD-L1 immune checkpoint showed sex and age associated differences. Bladders from healthy older female mice also showed a higher presence of tertiary lymphoid structures (TLSs) compared to both young female and male equivalents. Spatial immune profiling of N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN) carcinogen exposed male and female bladders from young and old mice revealed a similar frequency of TLS formation, sex differences in the bladder immune microenvironment and, age associated differences in latency of tumor induction. These findings support the incorporation of sex and age as factors in pre-clinical modeling of bladder cancer and will potentially advance the field of immunotherapeutic drug development to improve clinical outcomes.
Efficient 3D conformer generation of cyclic peptides formed by a disulfide bond
Authors: Tao Huanyu , Wu Qilong , Zhao Xuejun , Lin Peicong , Huang Sheng-You 
Published: May 2022

AbstractCyclic peptides formed by disulfide bonds have been one large group of common drug candidates in drug development. Structural information of a peptide is essential to understand its interaction with its target. However, due to the high flexibility of peptides, it is difficult to sample the near-native conformations of a peptide. Here, we have developed an extended version of our MODPEP approach, named MODPEP2.0, to fast generate the conformations of cyclic peptides formed by a disulfide bond. MODPEP2.0 builds the three-dimensional (3D) structures of a cyclic peptide from scratch by assembling amino acids one by one onto the cyclic fragment based on the constructed rotamer and cyclic backbone libraries. Being tested on a data set of 193 diverse cyclic peptides, MODPEP2.0 obtained a considerable advantage in both accuracy and computational efficiency, compared with other sampling algorithms including PEP-FOLD, ETKDG, and modified ETKDG (mETKDG). MODPEP2.0 achieved a high sampling accuracy with an average C$$\alpha$$
α
RMSD of 2.20 Å and 1.66 Å when 10 and 100 conformations were considered, respectively, compared with 3.41 Å and 2.62 Å for PEP-FOLD, 3.44 Å and 3.16 Å for ETKDG, 3.09 Å and 2.72 Å for mETKDG. MODPEP2.0 also reproduced experimental peptide structures for 81.35% of the test cases when an ensemble of 100 conformations were considered, compared with 54.95%, 37.50% and 50.00% for PEP-FOLD, ETKDG, and mETKDG. MODPEP2.0 is computationally efficient and can generate 100 peptide conformations in one second. MODPEP2.0 will be useful in sampling cyclic peptide structures and modeling related protein-peptide interactions, facilitating the development of cyclic peptide drugs.