bluuebunny/crossref_metadata_2025 huggingface dataset:
Meta-learning prediction of physical and chemical properties of magnetized water and fertilizer based on LSTM
Authors: Nie Jing , Wang Nianyi , Li Jingbin , Wang Kang , Wang Hongkun
Published: November 2021

Background

Due to the high cost of data collection for magnetization detection of media, the sample size is limited, it is not suitable to use deep learning method to predict its change trend. The prediction of physical and chemical properties of magnetized water and fertilizer (PCPMWF) by meta-learning can help to explore the effects of magnetized water and fertilizer irrigation on crops.

Method

In this article, we propose a meta-learning optimization model based on the meta-learner LSTM in the field of regression prediction of PCPMWF. In meta-learning, LSTM is used to replace MAML’s gradient descent optimizer for regression tasks, enables the meta-learner to learn the update rules of the LSTM, and apply it to update the parameters of the model. The proposed method is compared with the experimental results of MAML and LSTM to verify the feasibility and correctness.

Results

The average absolute percentage error of the meta-learning optimization model of meta-learner LSTM is reduced by 0.37% compared with the MAML model, and by 4.16% compared with the LSTM model. The loss value of the meta-learning optimization model in the iterative process drops the fastest and steadily compared to the MAML model and the LSTM model. In cross-domain experiments, the average accuracy of the meta-learning optimized model can still reach 0.833.

Conclusions

In the case of few sample, the proposed model is superior to the traditional LSTM model and the basic MAML model. And in the training of cross-domain datasets, this model performs best.
Alcohol and illicit drug use among young people living with HIV compared to their uninfected peers from the Kenyan coast: prevalence and risk indicators
Authors: Nyongesa Moses K. , Mwangi Paul , Kinuthia Michael , Hassan Amin S. , Koot Hans M. , Cuijpers Pim , Newton Charles R. J. C. , Abubakar Amina
Published: November 2021

Background

In sub-Saharan Africa, there is paucity of research on substance use patterns among young people living with HIV (YLWH). To address the gap, we sought to: i) determine the prevalence of substance use, specifically alcohol and illicit drug use, among YLWH compared to their HIV-uninfected peers; ii) investigate the independent association between young people’s HIV infection status and substance use; iii) investigate the risk indicators for substance use among these young people.

Methods

Between November 2018 and September 2019, a cross-sectional study was conducted at the Kenyan coast recruiting 819 young people aged 18–24 years (407 HIV-positive). Alcohol and drug use disorders identification tests (AUDIT and DUDIT) were administered via audio computer-assisted self-interview alongside other measures. Logistic regression was used to determine substance use risk indicators.

Results

The point prevalence of current substance use was significantly lower among YLWH than HIV-uninfected youths: current alcohol use, 13% vs. 24%, p <  0.01; current illicit drug use, 7% vs. 15%, p <  0.01; current alcohol and illicit drug use comorbidity, 4 vs. 11%, p <  0.01. Past-year prevalence estimates for hazardous substance use were generally low among young people in this setting (< 10%) with no significant group differences observed. Being HIV-positive independently predicted lower odds of current substance use, but not hazardous substance use. There was overlap of some risk indicators for current substance use between young people with and without HIV including male sex, khat use and an experience of multiple negative life events, but risk indicators unique to either group were also identified. Among YLWH, none of the HIV-related factors was significantly associated with current substance use.

Conclusions

At the Kenyan coast, substance use is a reality among young people. The frequency of use generally appears to be low among YLWH compared to the HIV-uninfected peers. Substance use prevention initiatives targeting young people, regardless of HIV infection status, are warranted in this setting to avert their potential risk for developing substance use disorders, including dependence. The multifaceted intrapersonal and interpersonal factors that place young people at risk of substance use need to be addressed as part of the substance use awareness and prevention initiatives.
A scoping review of de-implementation frameworks and models
Authors: Walsh-Bailey Callie , Tsai Edward , Tabak Rachel G. , Morshed Alexandra B. , Norton Wynne E. , McKay Virginia R. , Brownson Ross C. , Gifford Sheyna
Published: November 2021

Background

Reduction or elimination of inappropriate, ineffective, or potentially harmful healthcare services and public health programs can help to ensure limited resources are used effectively. Frameworks and models (FM) are valuable tools in conceptualizing and guiding the study of de-implementation. This scoping review sought to identify and characterize FM that can be used to study de-implementation as a phenomenon and identify gaps in the literature to inform future model development and application for research.

Methods

We searched nine databases and eleven journals from a broad array of disciplines (e.g., healthcare, public health, public policy) for de-implementation studies published between 1990 and June 2020. Two raters independently screened titles and abstracts, and then a pair of raters screened all full text records. We extracted information related to setting, discipline, study design, methodology, and FM characteristics from included studies.

Results

The final search yielded 1860 records, from which we screened 126 full text records. We extracted data from 27 articles containing 27 unique FM. Most FM (n = 21) were applicable to two or more levels of the Socio-Ecological Framework, and most commonly assessed constructs were at the organization level (n = 18). Most FM (n = 18) depicted a linear relationship between constructs, few depicted a more complex structure, such as a nested or cyclical relationship. Thirteen studies applied FM in empirical investigations of de-implementation, while 14 articles were commentary or review papers that included FM.

Conclusion

De-implementation is a process studied in a broad array of disciplines, yet implementation science has thus far been limited in the integration of learnings from other fields. This review offers an overview of visual representations of FM that implementation researchers and practitioners can use to inform their work. Additional work is needed to test and refine existing FM and to determine the extent to which FM developed in one setting or for a particular topic can be applied to other contexts. Given the extensive availability of FM in implementation science, we suggest researchers build from existing FM rather than recreating novel FM.

Registration

Not registered
Check-rein technique for Achilles tendon elongation following conservative management for acute Achilles tendon ruptures: a two-year prospective clinical study
Authors: Maffulli Nicola , Oliva Francesco , Migliorini Filippo
Published: November 2021

Background

Following conservative management for acute Achilles tendon (AT) ruptures, the tendon may heal in continuity, and some patients may present with an elongated Achilles tendon–gastrosoleus complex. This study investigated the efficacy and feasibility of a novel minimally invasive technique, which we named “check-rein procedure”, in patients with intact and elongated AT following conservative management for AT ruptures.

Methods

All patients who underwent the check-rein procedure for elongation of the gastrosoleus–AT complex by one experienced surgeon were prospectively enrolled. The AT resting angle (ATRA) and AT rupture score (ATRS) were assessed at baseline and repeated at 2-year follow-up, as were calf circumference and isometric plantarflexion strength of both ankles.

Results

Forty-three patients (43 procedures) were analysed. The mean time elapsed from injury to surgery was 28.7 ± 7.9 weeks. The mean age at surgery was 38.5 ± 5.7 years. At the last follow-up, ATRS, ATRA, isometric strength difference, and calf circumference of the affected side were increased (P < 0.0001). The rate of the return to sport was 98% (42 of 43). No wound complications or rupture were experienced by any patient.

Conclusion

The check-rein technique for AT elongation after conservative management of AT tears is effective and feasible to restore tendon length and calf function. The surgical outcome was influenced by the preoperative performance status, and longer time elapsed from injury to surgery worsens the outcomes.
A new biomechanical classification system for split fractures of the humeral greater tuberosity: guidelines for surgical treatment
Authors: Liu Gang , Guo Xiaoguang , Zhao Qian , Qin Bo , Lu Junjie , Bao Dingsu , Fu Shijie
Published: November 2021

Background

Split fractures of the humeral greater tuberosity (HGT) are common injuries. Although there are numerous surgical treatments for these fractures, no classification system combining clinical and biomechanical characteristics has been presented to guide the choice of fixation method.

Methods

We created a standardised fracture of the HGT in 24 formalin-fixed cadavers. Six were left as single-fragment fractures (Group A), six were further prepared to create single-fragment with medium size full-thickness rotator cuff tear (FT-RCT) fractures (Group B), six were cut to create multi-fragment fractures (Group C), and six were cut to create multi-fragment with FT-RCT fractures (Group D). Each specimen was fixed with a shortened proximal humeral internal locking system (PHILOS) plate. The fixed fractures were subjected to load and load-to-failure tests and the differences between groups analysed.

Results

The mean load-to-failure values were significantly different between groups (Group A, 446.83 ± 38.98 N; Group B, 384.17 ± 36.15 N; Group C, 317.17 ± 23.32 N and Group D, 266.83 ± 37.65 N, P < 0.05). The load-to-failure values for fractures with a greater tuberosity displacement of 10 mm were significantly different between each group (Group A, 194.00 ± 29.23 N; Group B, 157.00 ± 29.97 N; Group C, 109.00 ± 17.64 N and Group D, 79.67.83 ± 15.50 N; P < 0.05). These findings indicate that fractures with a displacement of 10 mm have different characteristics and should be considered separately from other HGT fractures when deciding surgical treatment.

Conclusions

Biomechanical classification of split fractures of the HGT is a reliable method of categorising these fractures in order to decide surgical treatment. Our findings and proposed system will be a useful to guide the choice of surgical technique for the treatment of fractures of the HGT.
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

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

Background

The 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.

Methods

In 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.

Results

In 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.

Conclusion

To 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

Background

The 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.

Methods

The 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.

Results

The 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.

Conclusion

The 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

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

Sexual 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

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

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

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

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.
Augmentative and alternative communication intervention for in-patient individuals with post-stroke aphasia: study protocol of a parallel-group, pragmatic randomized controlled trial
Authors: Huang Li , Chen Szu-Han Kay , Xu Shutian , Wang Yongli , Jin Xing , Wan Ping , Sun Jikang , Tao Jiming , Zhang Sicong , Zhang Guohui , Shan Chunlei
Published: November 2021

Background

People with post-stroke aphasia commonly receive speech-language therapy (SLT) when they are admitted to hospitals. Commonly, these patients reported communication difficulties in in-patient settings. Augmentative and alternative communication (AAC) has been reported as an effective treatment approach to improve communication effectiveness, language performance, decreasing depression, and improving quality of life for this population. However, little evidence has demonstrated the use of AAC intervention (AACT) in early recovery from people with post-stroke aphasia in in-patient rehabilitation settings for improving these patients’ communication effectiveness. The pilot randomized controlled trial (RCT) will explore the effectiveness and feasibility of including AACT in regular SLT for in-patient people with post-stroke aphasia.

Method

This pilot RCT is a single-blind, randomized controlled trial with two parallel groups. Both groups receive a 1-h treatment session, including either both AACT and SLT or SLT only for ten consecutive days. We aim to include 22 in-patient participants with post-stroke aphasia in each group. Participants will be assessed at pre- and post-intervention and 2 weeks after intervention. The primary outcomes are the ability of communication measured by the communication of basic needs subtest in the Functional Assessment of Communication Skills for Adult (FACS) and the overall language performance measured by the Chinese Standard Aphasia Battery (ABC). The secondary outcomes include a 10-min conversation, the 10-item Hospital version of the Stroke Aphasic Depression Questionnaire (SADQH-10), the Stroke-Specific Quality of Life Scale (SS-QOL), and a patient and caregiver satisfaction questionnaire.

Discussion

This pilot RCT will contribute to new scientific evidence to the field of aphasia rehabilitation in early recovery during the in-patient period. The paper describes the trial, which will explore the effect of combining AACT and SLT and SLT only, our choice of primary and secondary outcome measures, and proposed analyses. The study results will provide information for implementing AACT in the regular in-patient SLT of future RCTs.

Trial registration

Chinese Clinical Trial Registry database (ChiCTR) ChiCTR2000028870. Registered on 5 January 2020
The ACAMTO study—impact of add-on osteopathic treatment on adolescent patients with anorexia nervosa: study protocol for a randomized controlled trial
Authors: Letranchant Aurélie , Montebello Yunkyung Kim-de , bigre Corinne Dugré-Le , Wagner Agathe , Curt Florence , Silva Jérôme , Nicolas Isabelle , Votadoro Pablo , Kalindjian Nina , Korchonnoff Anna , Gutierre Andréa , Novelli Ana Beatriz , Pham-Scottez Alexandra , Corcos Maurice
Published: November 2021

Background

Anorexia nervosa (AN) mainly affects women (sex ratio 1/10) and most often starts during adolescence. The prognosis of AN remains poor (10% of deaths and high risk of chronicity). Body dissatisfaction, disturbances in recognition and identification of body sensations are some of the key symptoms of AN. However, there is a contrast between this consensual observation of body image disorders in AN, and the relative deficit of specifically targeted body treatments. Our proposal for a body approach specifically dedicated to AN is based on the understanding that posture, breathing, muscle tension and body perception are closely linked to our psychological and emotional state and are therefore disturbed in patients with AN. The purpose of this monocentric randomized controlled trial is to evaluate if a targeted osteopathic protocol treatment for AN in addition to treatment as usual (TAU) is significantly more effective than TAU alone.

Methods

In total, 72 patients meeting the inclusion criteria will be randomly assigned to one of the two treatment groups: one receiving the specific osteopathic treatment targeted for AN in addition to the TAU (group A) and the other one, receiving TAU only (group B). The patients in group A will receive 5 30-min osteopathic treatment sessions. Soft specific palpatory techniques on the diaphragm, digestive system and cervical region will be performed. The TAU is defined by the multidisciplinary approach recommended by the French health high authority. The primary outcome is the evaluation of interoceptive sensibility and secondary outcomes include clinical and psychopathology-related symptoms with assessment of somatic dysfunctions’ evolution. A qualitative study will also be carried out, applying the Interpretative Phenomenological Analysis method. Patients will be included for a maximum of 14 weeks between the inclusion time and the last evaluation.

Discussion

If the results of the study are positive (statistically significant efficacy of this osteopathic treatment protocol), the study will provide arguments in favor of osteopathic sessions as a possible non-invasive additional treatment option in the multidisciplinary care approach for patients with AN.

Trial registration

ClinicalTrials.gov ID: NCT04666415, Release Date: December 11, 2020; N° ID-RCB: 2019-A02613-54.
Genetic diversity and immunogenicity of the merozoite surface protein 1 C-terminal 19-kDa fragment of Plasmodium ovale imported from Africa into China
Authors: Xu Qinwen , Liu Sihong , Kassegne Kokouvi , Yang Bo , Lu Jiachen , Sun Yifan , Zhong Wenli , Zhang Miaosa , Liu Yaobao , Zhu Guoding , Cao Jun , Cheng Yang
Published: November 2021

Background

Merozoite surface protein 1 (MSP1) plays an essential role in erythrocyte invasion by malaria parasites. The C-terminal 19-kDa region of MSP1 has long been considered one of the major candidate antigens for a malaria blood-stage vaccine against Plasmodium falciparum. However, there is limited information on the C-terminal 19-kDa region of Plasmodium ovale MSP1 (PoMSP119). This study aims to analyze the genetic diversity and immunogenicity of PoMSP119.

Methods

A total of 37 clinical Plasmodium ovale isolates including Plasmodium ovale curtisi and Plasmodium ovale wallikeri imported from Africa into China and collected during the period 2012–2016 were used. Genomic DNA was used to amplify P. ovale curtisi (poc) msp119 (pocmsp119) and P. ovale wallikeri (pow) msp119 (powmsp119) genes by polymerase chain reaction. The genetic diversity of pomsp119 was analyzed using the GeneDoc version 6 programs. Recombinant PoMSP119 (rPoMSP119)-glutathione S-transferase (GST) proteins were expressed in an Escherichia coli expression system and analyzed by western blot. Immune responses in BALB/c mice immunized with rPoMSP119-GST were determined using enzyme-linked immunosorbent assay. In addition, antigen-specific T cell responses were assessed by lymphocyte proliferation assays. A total of 49 serum samples from healthy individuals and individuals infected with P. ovale were used for the evaluation of natural immune responses by using protein microarrays.

Results

Sequences of pomsp119 were found to be thoroughly conserved in all the clinical isolates. rPoMSP119 proteins were efficiently expressed and purified as ~ 37-kDa proteins. High antibody responses in mice immunized with rPoMSP119-GST were observed. rPoMSP119-GST induced high avidity indexes, with an average of 92.57% and 85.32% for rPocMSP119 and rPowMSP119, respectively. Cross-reactivity between rPocMSP119 and rPowMSP119 was observed. Cellular immune responses to rPocMSP119 (69.51%) and rPowMSP119 (52.17%) induced in rPocMSP119- and rPowMSP119-immunized mice were found in the splenocyte proliferation assays. The sensitivity and specificity of rPoMSP119-GST proteins for the detection of natural immune responses in patients infected with P. ovale were 89.96% and 75%, respectively.

Conclusions

This study revealed highly conserved gene sequences of pomsp119. In addition, naturally acquired humoral immune responses against rPoMSP1 were observed in P. ovale infections, and high immunogenicity of rPoMSP119 in mice was also identified. These instructive findings should encourage further testing of PoMSP119 for rational vaccine design.

Graphical abstract
Functional characterization of two clip domain serine proteases in innate immune responses of Aedes aegypti
Authors: Wang Hao-Cheng , Wang Qiu-Hui , Bhowmick Biswajit , Li Yi-Xun , Han Qian
Published: November 2021

Background

Clip domain serine proteases (CLIPs), a very diverse group of proteolytic enzymes, play a crucial role in the innate immunity of insects. Innate immune responses are the first line of defense in mosquitoes against the invasion of pathogenic microorganisms. The Toll pathway, immunodeficiency (IMD) pathway and melanization are the main processes of innate immunity inAedes aegypti. CLIPS are classified into five subfamilies—CLIPA, CLIPB, CLIPC, CLIPD, and CLIPE—based on their sequence specificity and phylogenetic relationships. We report the functional characterization of the genes that code for two CLIPs inAe. aegypti(Ae):Ae-CLIPB15andAe-CLIPB22.

Methods

Clustal Omega was used for multiple amino acid sequence alignment ofAe-CLIPB15andAe-CLIPB22with differentCLIPgenes from other insect species. The spatiotemporal expression profiles ofAe-CLIPB15andAe-CLIPB22were examined. We determined whetherAe-CLIPB15andAe-CLIPB22respond to microbial challenge and tissue injury. RNA interference (RNAi) was used to explore the function ofAe-CLIPB15andAe-CLIPB22in the defense ofAe. aegyptiagainst bacterial and fungal infections. The expression levels of nuclear factor kappa B (NF-κB) transcription factorsREL1andREL2in the Toll pathway and IMD pathway after bacterial infection were investigated. Finally, the change in phenoloxidase (PO) activity inAe-CLIPB15andAe-CLIPB22knockdown adults was investigated.

Results

We performed spatiotemporal gene expression profiling ofAe-CLIPB15andAe-CLIPB22genes inAe.aegyptiusing quantitative real-time polymerase chain reaction. These genes were expressed in different stages and tissues. The messenger RNA (mRNA) levels for both genes were also up-regulated by Gram-negative bacteriaEscherichia coli, Gram-positive bacteriaStaphylococcus aureusand fungalBeauveria bassianainfections, as well as in the tissue injury experiments. RNAi-mediated knockdown ofAe-CLIPB15led to a significant decrease of PO activity in the hemolymph ofAe. aegypti, while other RNAi experiments revealed that bothAe-CLIPB15andAe-CLIPB22were involved in immune defense against bacterial and fungal infections. The mRNA expression of NF-κB transcription factorsREL1andREL2in the Toll pathway and IMD pathway differed betweenAe-CLIPB15andAe-CLIPB22knockdown mosquitoes infected with bacteria and wild type mosquitoes infected with bacteria.

Conclusions

Our findings suggest thatAe-CLIPB15andAe-CLIPB22play a critical role in mosquito innate immunity, and that they are involved in immune responses to injury and infection. Their regulation of transcription factors and PO activity indicates that they also play a specific role in the regulation of innate immunity.

Graphical Abstract
Development of a chemogenomics library for phenotypic screening
Authors: Dafniet Bryan , Cerisier Natacha , Boezio Batiste , Clary Anaelle , Ducrot Pierre , Dorval Thierry , Gohier Arnaud , Brown David , Audouze Karine , Taboureau Olivier
Published: November 2021

With the development of advanced technologies in cell-based phenotypic screening, phenotypic drug discovery (PDD) strategies have re-emerged as promising approaches in the identification and development of novel and safe drugs. However, phenotypic screening does not rely on knowledge of specific drug targets and needs to be combined with chemical biology approaches to identify therapeutic targets and mechanisms of actions induced by drugs and associated with an observable phenotype. In this study, we developed a system pharmacology network integrating drug-target-pathway-disease relationships as well as morphological profile from an existing high content imaging-based high-throughput phenotypic profiling assay known as “Cell Painting”. Furthermore, from this network, a chemogenomic library of 5000 small molecules that represent a large and diverse panel of drug targets involved in diverse biological effects and diseases has been developed. Such a platform and a chemogenomic library could assist in the target identification and mechanism deconvolution of some phenotypic assays. The usefulness of the platform is illustrated through examples.
Alpha-synuclein from patient Lewy bodies exhibits distinct pathological activity that can be propagated in vitro
Authors: Marotta Nicholas P. , Ara Jahan , Uemura Norihito , Lougee Marshall G. , Meymand Emily S. , Zhang Bin , Petersson E. James , Trojanowski John Q. , Lee Virginia M.-Y.
Published: November 2021

Lewy bodies (LBs) are complex, intracellular inclusions that are common pathological features of many neurodegenerative diseases. They consist largely of aggregated forms of the protein alpha-Synuclein (α-Syn), which misfolds to give rise to beta-sheet rich amyloid fibrils. The aggregation of monomers into fibrils occurs readily in vitro and pre-formed fibrils (PFFs) generated from recombinant α-Syn monomers are the basis of many models of LB diseases. These α-Syn PFFs recapitulate many pathological phenotypes in both cultured cells and animal models including the formation of α-Syn rich, insoluble aggregates, neuron loss, and motor deficits. However, it is not clear how closely α-Syn PFFs recapitulate the biological behavior of LB aggregates isolated directly from patients. Direct interrogation of the cellular response to LB-derived α-Syn has thus far been limited. Here we demonstrate that α-Syn aggregates derived from LB disease patients induce pathology characterized by a prevalence of large somatic inclusions that is distinct from the primarily neuritic pathology induced by α-Syn PFFs in our cultured neuron model. Moreover, these LB-derived aggregates can be amplified in vitro using recombinant α-Syn to generate aggregates that maintain the unique, somatic pathological phenotype of the original material. Amplified LB aggregates also showed greater uptake in cultured neurons and greater pathological burden and more rapid pathological spread in injected mouse brains, compared to α-Syn PFFs. Our work indicates that LB-derived α-Syn from diseased brains represents a distinct conformation species with unique biological activities that has not been previously observed in fully recombinant α-Syn aggregates and demonstrate a new strategy for improving upon α-Syn PFF models of synucleinopathies using amplified LBs.