bluuebunny/crossref_metadata_2025_split huggingface dataset:
Aloin induced apoptosis by enhancing autophagic flux through the PI3K/AKT axis in osteosarcoma
Authors: He Jiaming , Zhang Wenkan , Zhou Xiaozhong , Yan Weiqi , Wang Zhan 
Published: November 2021

Abstract
Background
Osteosarcoma is a malignant tumor of bone and soft tissue in adolescents. Due to its tumor biological behavior pattern, osteosarcoma usually generates poor prognosis. Autophagy is an important self-defense mechanism in osteosarcoma.

Methods
Cell viability in IC50 testing and reverse assays was examined by the MTT assay. Cell apoptosis conditions were examined by flow cytometry, Hoechst 33,342 staining and apoptosis-related protein immunoblotting. Autophagy conditions were tested by autophagy-related protein immunoblotting, transmission electron microscopic observation and dual fluorescence autophagy flux detection. The possible targets of aloin were screened out by network pharmacology and bioinformatic methods. Osteosarcoma xenografts in nude BALB/c mice were the model for in vivo research on tumor suppression, autophagy induction, pathway signaling and toxicity tests. In vivo bioluminescence imaging systems, immunohistochemical assays, and gross tumor volume comparisons were applied as the main research methods in vivo.

Results
Aloin induced osteosarcoma apoptosis in a dose-dependent manner. Its possible effects on the PI3K/AKT pathway were screened out by network pharmacology methods. Aloin increased autophagic flux in osteosarcoma by downregulating the PI3K/AKT pathway. Aloin promoted autophagic flux in the osteosarcoma cell lines HOS and MG63 in a dose-dependent manner by promoting autophagosome formation. Chloroquine reversed the apoptosis-promoting and autophagy-enhancing effects of aloin. Autophagy induced by starvation and rapamycin significantly enhanced the autophagic flux and apoptosis induced by aloin, which verified the role of the PI3K/AKT axis in the pharmacological action of aloin. Therapeutic effects, autophagy enhancement and regulatory effects on the PI3K/AKT/mTOR pathway were demonstrated in a nude mouse xenogeneic osteosarcoma transplantation model.

Conclusions
Aloin inhibited the proliferation of osteosarcoma by inhibiting the PI3K/AKT/mTOR pathway, increasing autophagic flux and promoting the apoptosis of osteosarcoma cells.
Potentials and current shortcomings in the cooperation between German centers for rare diseases and primary care physicians: results from the project TRANSLATE-NAMSE
Authors: Druschke D. , Krause F. , Müller G. , Scharfe J. , Hoffmann G. F. , Schmitt J. ,   TRANSLATE-NAMSE-Consortium
Published: November 2021

AbstractBackgroundThe TRANSLATE-NAMSE project with the strengthening of the centers for rare diseases with their affiliation to the European Reference Networks was a major step towards the implementation of the German National Plan of Action for People with Rare Diseases establishing better care structures. As primary care physicians, general practitioners and pediatricians play a central role in the diagnosis of patients with rare disease, as it is usually them referring to specialists and rare disease centers. Therefore, the interface management between primary care physicians and the centers for rare diseases is of particular importance.MethodsIn a mixed-method-approach an anonymous postal survey of 1,500 randomly selected primary care physicians in Germany was conducted with focus on (1)knowledgeabout a center for rare diseases and how it works, (2) in case of cooperation,satisfactionwith the services provided by centers, and (3)expectations and needsthey have with regard to the centers. In addition, in-depth telephone interviews were conducted with physicians who had already referred patients to a center.ResultsIn total, 248 physicians responded to the survey, and 15 primary care physicians were interviewed. We observed a wide lack of knowledge about the existence of (45.6% confirmed to know at least one center) about how to access rare disease centers (50.4% of those who know a center confirmed knowledge) and what the center specializes in. In case of cooperation the evaluation was mostly positive.ConclusionTo improve medical care, the interplay between primary care physicians and rare disease centers needs to be strengthened. (1) To improve the communication, the objectives and functioning of the rare disease centers should become more visible. (2) Other projects dealing with the analysis and improvement of interface management between centers and primary care physicians, as described in the National Plan of Action for People with Rare Diseases, need to be implemented immediately. (3) If the project is evaluated positively, the structures of TRANSLATE-NAMSE should be introduced nationwide into the German health care system to ensure comprehensive, quality-assured care for people with rare diseases with special consideration of the key role of primary care physicians—also taking into account the financial expenditures of this new care model.
Overlap phenotypes of the left ventricular noncompaction and hypertrophic cardiomyopathy with complex arrhythmias and heart failure induced by the novel truncated DSC2 mutation
Authors: Lin Yubi , Huang Jiana , Zhu Zhiling , Zhang Zuoquan , Xian Jianzhong , Yang Zhe , Qin Tingfeng , Chen Linxi , Huang Jingmin , Huang Yin , Wu Qiaoyun , Hu Zhenyu , Lin Xiufang , Xu Geyang 
Published: November 2021

AbstractBackgroundThe left ventricular noncompaction cardiomyopathy (LVNC) is a rare subtype of cardiomyopathy associated with a high risk of heart failure (HF), thromboembolism, arrhythmia, and sudden cardiac death.MethodsThe proband with overlap phenotypes of LVNC and hypertrophic cardiomyopathy (HCM) complicates atrial fibrillation (AF), ventricular tachycardia (VT), and HF due to the diffuse myocardial lesion, which were diagnosed by electrocardiogram, echocardiogram and cardiac magnetic resonance imaging. Peripheral blood was collected from the proband and his relatives. DNA was extracted from the peripheral blood of proband for high-throughput target capture sequencing. The Sanger sequence verified the variants. The protein was extracted from the skin of the proband and healthy volunteer. The expression difference of desmocollin2 was detected by Western blot.ResultsThe novel heterozygous truncated mutation (p.K47Rfs*2) of theDSC2gene encoding an important component of desmosomes was detected by targeted capture sequencing. The western blots showed that the expressing level of functional desmocollin2 protein (~ 94kd) was lower in the proband than that in the healthy volunteer, indicating thatDSC2p.K47Rfs*2 obviously reduced the functional desmocollin2 protein expression in the proband.ConclusionThe heterozygousDSC2p.K47Rfs*2 remarkably and abnormally reduced the functional desmocollin2 expression, which may potentially induce the overlap phenotypes of LVNC and HCM, complicating AF, VT, and HF.
The impact of water depth and speed on muscle fiber activation of healthy dogs walking in a water treadmill
Authors: Vitger Anne Désiré , Bruhn-Rasmussen Tanja , Pedersen Eja Oppenlænder , Fuglsang-Damgaard Lene Høeg , Harrison Adrian Paul 
Published: November 2021

Abstract
Background
Water treadmills are frequently used in the rehabilitation of dogs, for example with the purpose of re-building muscular strength after surgery. However, little is known about how different water depths and velocities affect the muscular workload during aquatic locomotion. This study used acoustic myography to assess hind limb muscle fiber activation in 25 healthy large-breed dogs walking in a water treadmill. Acoustic myography sensors were attached to the skin over the vastus lateralis of the quadriceps and the biceps femoris muscles. The dogs walked at two velocities (30 and 50 m/min) and four water depths: bottom of the pads, hock, stifle and mid-femur. Acoustic myograph signals were analyzed for changes in three muscle function parameters: efficiency/coordination (E-score) and spatial (S-score) and temporal (T-score) summation.

Results
Differences between E, S, and T were statistically significant compared across different speeds (30, 50) and water levels (0, 1, 2, 3) using a one-way ANOVA with multiple comparisons (Tukey; Geisser-Greenhouse correction) as well as a two-tailed one sample t-test. At 50 m/min in water at the mid-femur, the biceps femoris was less efficient (P < 0.001) and recruited more fibers (P = 0.01) at a higher firing rate (P = 0.03) compared to working in shallower water, while the vastus lateralis was also less efficient (P < 0.01), but spatial and temporal summation did not change significantly. At 30 m/min, biceps efficiency was reduced (P < 0.01) when water was at the mid-femur compared to the bottom of the pads level. Walking in stifle- or hock-deep water did not show increased muscle activation for either muscle compared to walking in water at the bottom of the pads.

Conclusion
More muscle activation was required to walk in water at a depth at the level of the mid-femur compared to shallower water, and this exercise was more demanding for the biceps femoris, a muscle engaged in propulsion, than for vastus lateralis. These findings may help practitioners towards making more precise rehabilitation protocols.
The impact of interventions to reduce risk and incidence of intimate partner violence and sexual violence in conflict and post-conflict states and other humanitarian crises in low and middle income countries: a systematic review
Authors: Spangaro Jo , Toole-Anstey Chye , MacPhail Catherine L. , Rambaldini-Gooding Delia C. , Keevers Lynne , Garcia-Moreno Claudia 
Published: November 2021

AbstractSexual violence and intimate partner violence are exacerbated by armed conflict and other humanitarian crises. This narrative systematic review of evidence for interventions to reduce risk and incidence of sexual and intimate partner violence in conflict, post-conflict and other humanitarian crises, updates and expands our review published in 2013. A search of ten bibliographic databases for publications from January 2011 to May 2020 used database specific key words for sexual/intimate partner violence and conflict/humanitarian crisis. The 18 papers, describing 16 studies were undertaken in conflict/post-conflict settings in 12 countries. Six intervention types were reported: i) personnel; ii) community mobilisation; iii) social norms; iv) economic empowerment; v) empowerment; and vi) survivor responses, with the most common being economic empowerment (n = 7) and gendered social norms interventions (n = 6). Combined interventions were reported in nine papers. Four studies identified non-significant reductions in incidence of sexual/ intimate partner violence, showing an evident positive trend; all four evaluated gendered social norms or economic empowerment singly or in combination. Evidence for improved mental health outcomes was found for some economic empowerment, social norms and survivor interventions. Some evidence of reduced risk of sexual violence and intimate partner violence was identified for all intervention types. Qualitative studies suggest that experiences of social connection are important for women who participate in programming to address sexual and intimate partner violence. Interventions with multiple strategies appear to hold merit. Achieving and demonstrating reduced sexual and intimate partner violence remains challenging in this context. Future research should continue to explore how social norms interventions can be most effectively delivered, including the impact of including mixed and same sex groups. Work is needed with local partners to ensure programs are contextually adapted.
The role of social capital in women’s sexual and reproductive health and rights in humanitarian settings: a systematic review of qualitative studies
Authors: Ireland Hannah , Tran Nguyen Toan , Dawson Angela 
Published: November 2021

Abstract
Background
Social capital is an important social determinant of women’s sexual and reproductive health and rights. Little research has been conducted to understand the role of social capital in women’s sexual and reproductive health and how this can be harnessed to improve health in humanitarian settings. We synthesised the evidence to examine the nexus of women’s sexual and reproductive health and rights and social capital in humanitarian contexts.

Methods
We undertook a systematic review of qualitative studies. The preferred reporting items for systematic review and meta-analysis guidelines were used to identify peer-reviewed, qualitative studies conducted in humanitarian settings published since 1999. We searched CINAHL, MEDLINE, ProQuest Health & Medicine, PubMed, Embase and Web of science core collection and assessed quality using the Critical Appraisal Skills Programme tool. We used a meta-ethnographic approach to synthesise and analyse the data.

Findings
Of 6749 initially identified studies, we included 19 studies, of which 18 were in conflict-related humanitarian settings and one in a natural disaster setting. The analysis revealed that the main form of social capital available to women was bonding social capital or strong links between people within groups of similar characteristics. There was limited use of bridging social capital, consisting of weaker connections between people of approximately equal status and power but with different characteristics. The primary social capital mechanisms that played a role in women’s sexual and reproductive health and rights were social support, informal social control and collective action. Depending on the nature of the values, norms and traditions shared by network members, these social capital mechanisms had the potential to both facilitate and hinder positive health outcomes for women.

Conclusions
These findings demonstrate the importance of understanding social capital in planning sexual and reproductive health responses in humanitarian settings. The analysis highlights the need to investigate social capital from an individual perspective to expose the intra-network dynamics that shape women’s experiences. Insights could help inform community-based preparedness and response programs aimed at improving the demand for and access to quality sexual and reproductive health services in humanitarian settings.
Survey of non-conventional mental health care facilities in Côte d’Ivoire: first stage
Authors: Koua Asseman Médard , Djo Bi Djo François , Kouadio Raymond N’Guessan , Coulibaly Zoumana , Sreu Eric , Konandri Eméric Désiré , Koua Aka N’zi Jean Vincent , Huppertz Sharon , Heetderks Gesine , Huppertz Michael 
Published: November 2021

Abstract
Background
Mental illnesses and disabilities as well as epileptic diseases remain an important public health issue. In Côte d’Ivoire, the provision of psychiatric care and specialised psychosocial facilities is almost non-existent. This study is based on the hypothesis that the care of people suffering from mental illness and epilepsy in Côte d’Ivoire is mainly in the hands of non-conventional mental health care facilities, including so-called ‘Prayer Camps’. These work according to traditional and spiritual principles and are mostly not registered or controlled by the Ivorian authorities.

Methods
This study is the first stage of a multi-stage study. For the first stage, a quantitative method with an exploratory and descriptive aim was chosen. 541 non-conventional mental health care facilities in Côte d’Ivoire were mapped, typologised according to their spiritual orientation and treatment methods, and examined according to some charactersitics. Semi-structured interviews with 435 facility leaders were conducted.

Results
The article provides a typology of four types of non-conventional mental health care facilities in Côte d’Ivoire including Christian Prayer Camps, Traditional Healing Centres, Phytotherapy Centres, and Roqya Centres. It explores their administrative embedding, the qualification of the facility leaders as well as their willingness, in principle, to cooperate with conventional mental health care centres. A considerable number of non-conventional expressed a desire or acceptance of cooperation with psychiatric organisations.

Conclusions
The next stage of this multi-stage study will be to assess the clinical and legal situation of the patients in these centres. The aim is to interview the patients in order to analyse their perceptions and to capture the concerns of relatives and staff in the centres as well as the human rights situation in a mixed-method study. The long-term objective is to establish future cooperation between conventional psychiatric care providers and suitable non-conventional mental health care facilities and to implement a community mental health care policy in Côte d’Ivoire.
The frequent and clinically benign anomalies of chromosomes 7 and 20 in Shwachman-diamond syndrome may be subject to further clonal variations
Authors: Khan Abdul Waheed , Kennedy Alyssa , Furutani Elissa , Myers Kasiani , Frattini Annalisa , Acquati Francesco , Roccia Pamela , Micheloni Giovanni , Minelli Antonella , Porta Giovanni , Cipolli Marco , Cesaro Simone , Danesino Cesare , Pasquali Francesco , Shimamura Akiko , Valli Roberto 
Published: November 2021

Abstract
Background
An isochromosome of the long arm of chromosome 7, i(7)(q10), and an interstitial deletion of the long arm of chromosome 20, del(20)(q), are the most frequent anomalies in the bone marrow of patients with Shwachman-Diamond syndrome, which is caused in most cases by mutations of the SBDS gene. These clonal changes imply milder haematological symptoms and lower risk of myelodysplastic syndromes and acute myeloid leukaemia, thanks to already postulated rescue mechanisms.

Results
Bone marrow from fourteen patients exhibiting either the i(7)(q10) or the del(20)(q) and coming from two large cohorts of patients, were subjected to chromosome analyses, Fluorescent In Situ Hybridization with informative probes and array-Comparative Genomic Hybridization. One patient with the i(7)(q10) showed a subsequent clonal rearrangement of the normal chromosome 7 across years. Four patients carrying the del(20)(q) evolved further different del(20)(q) independent clones, within a single bone marrow sample, or across sequential samples. One patient with the del(20)(q), developed a parallel different clone with a duplication of chromosome 3 long arm. Eight patients bore the del(20)(q) as the sole chromosomal abnormality. An overall overview of patients with the del(20)(q), also including cases already reported, confirmed that all the deletions were interstitial. The loss of material varied from 1.7 to 26.9 Mb and resulted in the loss of the EIF6 gene in all patients.

Conclusions
Although the i(7)(q) and the del(20)(q) clones are frequent and clinically benign in Shwachman Diamond-syndrome, in the present work we show that they may rearrange, may be lost and then reconstructed de novo, or may evolve with independent clones across years. These findings unravel a striking selective pressure exerted by SBDS deficiency driving to karyotype instability and to specific clonal abnormalities.
Using a WeChat mini-program-based lactation consultant intervention to increase the consumption of mother’s own milk by preterm infants in the neonatal intensive care unit: a study protocol for a cluster randomized controlled trial
Authors: Huo Jie , Wu Xinping , Gu Chuanli , Yu Zhangbin , Zhang Jun , Chen Xiaohui , Zhu Jingai , Liu Feng , Liu Beibei , Li Qianqian , Han Shuping 
Published: November 2021

Abstract
Background
The benefits of mother’s own milk (MOM) for preterm infants have been widely recognized. Many studies have shown that the rate of breastfeeding of premature infants remains very low. Although many studies use measures to promote breastfeeding, few high-quality cluster randomized controlled studies have evaluated the effectiveness of these measures. WeChat is an instant messaging software for smart terminals, and WeChat mini-programs have been widely used to promote health and self-management in China. Based on this background, we designed a randomized controlled study based on WeChat mini-programs to promote MOM feeding of premature infants in the neonatal intensive care unit (NICU).

Methods/design
This study will evaluate the effectiveness of WeChat mini-programs to increase the consumption of MOM feeding in twelve NICUs in Jiangsu Province, namely, six “intervention” NICUs and six “control” NICUs. The study process is as follows: (1) design and preparation, (2) NICU recruitment and training, (3) interpretation and analysis of baseline data, (4) quality control implementation process, and (5) data analysis feedback and publication of study reports. The primary outcome is the proportion of MOM feeding of premature infants during NICU hospitalization. The secondary outcomes are as follows: (1) time to initiation of MOM feeding (hours) and proportion of first-time MOM feeding (%), (2) duration of parenteral nutrition (days), (3) time to total gastrointestinal feeding (days), (4) hospitalization time and hospitalization cost, and (5) incidence of complications (necrotizing enterocolitis, bronchopulmonary dysplasia, feeding intolerance, late-onset sepsis, retinopathy of prematurity).

Discussion
This study is the first cluster randomized controlled trial on the intervention of using a WeChat mini-program-based lactation consultant for premature infants in the NICU in China. We hope this study can improve the consumption of MOM by NICU premature infants during hospitalization through the intervention of WeChat mini-programs.

Trial registration
ClinicalTrials.gov NCT04383379. Registered on May 5, 2020.