bluuebunny/crossref_metadata_2025 huggingface dataset:
Risk factors for twin pregnancy in women undergoing double cleavage embryo transfer
Authors: Chen Panpan , Hu Kai-Lun , Jin Jiani , Chen Ruixue , Xu Qiqi , Zhao Wei , Zhang Runju , Xing Lanfeng , Zhu Yimin , Zhang Dan
Published: March 2022

Background

Two or more embryo transfers have been used to increase the success rate of live birth in traditional in vitro fertilization (IVF) strategy at the expense of increased risks of multiple pregnancy and adverse perinatal outcomes. The decision regarding the elective single embryo transfer or double embryo transfer remains inconclusive. The aim of this study was to investigate the risk factors for twin pregnancy in IVF.

Methods

Participants who underwent their first fresh IVF cycle where two cleavage stage embryos were transferred in Women’s Hospital of Zhejiang University between January 2010 and December 2018 were included in this retrospective cohort study. The primary outcome was twin delivery. Secondary outcomes included preterm birth and low birth weight

Results

Fifteen thousand four hundred fifty-nine women were available for final analysis, in which 1511 women resulted in twin delivery and 4788 women had singleton delivery. Female age over 35 was associated with reduced rates of twin pregnancy compared with female age at or less than 35 (9.5% vs 25.1%, aRR = 0.38 (0.27. 0.55)). Poor-type endometrium was associated with reduced rates of twin pregnancy (19.2% vs 27.5%, aRR = 0.75 (0.58. 0.96)). Two good-quality embryos for transfer was associated with significantly higher rates of twin pregnancy compared with one good-quality or none good-quality embryo (26% vs 12.8% vs 9.3%, aRR = 0.56 (0.45. 0.70), aRR = 0.44(0.26. 0.74)). Female age over 35 and none or one good-quality embryo for transfer were associated with reduced rate of low birth weight and preterm birth.

Conclusion

Women with age over 35, poor-type endometrium, one good-quality embryo or none good-quality embryo were associated with reduced rate for twin pregnancy.
Evaluation of a breastfeeding promotion film among a racially minoritized sample
Authors: Blackman Kacie C. A. , Slama Derek S. , Pickering Trevor A. , Russell Aqueelah , Valentine Wenonah , Merchant Meridith A. , Saetermoe Carrie
Published: March 2022

Background

In Los Angeles County (LAC), disparities in breastfeeding rates vary by race and region. Black persons are more affected by social and environmental factors than other racial/ethnic groups, leading to lower breast/chestfeeding rates. This study aims to evaluate the community’s knowledge, perceptions, experiences, barriers, and solutions before and after an educational film about Black persons who are breast/chestfeeding.

Methods

Participant responses were collected anonymously through an online survey (via QR code) pre-and post-viewing a film with open- and closed-ended questions. There were 15 pre-screening questions and 24 post-screening questions discussed with a team of community experts. Questions included four main areas related to breast/chestfeeding: current/past experiences, support, awareness of laws, and solutions. Central tendency, variance, and paired differences were calculated from evaluation responses.

Results

There were 185 participants who completed the pre-screening evaluation and 57 participants who completed the post-screening evaluation. Racial/ethnic differences were found for stated reasons for attendance, and perceptions of breastfeeding being challenging after viewing the video. On a five-point Likert scale (1 = very relevant, 5 = not relevant), most participants felt the video was relevant (median response = “2-relevant”; IQR = “3-neutral”; “1-very relevant”), learned something new (81.4%) and knew how to access breast/chestfeeding support after viewing the video (93.2%).

Conclusions

Current media is a way to alter perceptions and opinions, and provides information. Additionally, it can be a way of increasing awareness of issues that Black breast/chestfeeding persons encounter. Strategic marketing efforts for future film screenings may increase attendance of those that can gain insight into breast/chestfeeding support (youth/young adults and males). Supportive breast/chestfeeding environments can also be a reality with readily accessible, unified, and encouraging personal and professional networks.
A pilot study of game-based learning programs for childhood cancer survivors
Authors: Masumoto Daisuke , Nakagami-Yamaguchi Etsuko , Nambu Misako , Maeda Miho , Uryu Hideko , Hayakawa Akira , Linn Zayar , Okamura Satoshi , Kurihara Kosuke , Kihira Kentaro , Deguchi Takao , Hori Hiroki
Published: March 2022

Background

Childhood cancer survivors lacking awareness on their potential risks of late effects often fail to seek adequate follow-up care. Patient education matching their preference is of great importance to improve their adherence to survivorship care. In this study, we developed two age-dependent game-based learning programs, which enable continuous approaches for childhood cancer survivors along their intellectual maturation. Then, we assessed the effectiveness of the programs.

Methods

Childhood cancer survivors over 10 years of age who regularly visited a long-term follow-up clinic were enrolled in this study. They were requested to play either of two different types of game tools, one for school children and another for adolescents and young adults, for one month at home. To evaluate the educational effects of the programs, they were examined for health management awareness, self-esteem, and knowledge on cancer-related late effects before and after the intervention with age-based questionnaires and knowledge tests.

Results

Among 83 participants, 49 (59.0%) completed the assessments over the period of 12 months. The health management awareness and knowledge levels increased significantly at 1-month after the intervention as compared to the baseline in both school children and adolescents/young adults (for health management awareness, p = 0.011 in elementary school children; p = 0.007 in junior high school children; p < 0.001 in adolescents/young adults; for knowledge levels, p < 0.001 in school children; p < 0.001 in adolescents/young adults). The effect was maintained for 12 months in school children while it decreased in adolescents and young adults with time. Self-esteem significantly increased at 1-month (p = 0.002 in school children; p = 0.020 in adolescents/young adults) and was maintained for 12 months in both age groups.

Conclusion

The game-based learning programs enhanced health locus of control and self-esteem in childhood cancer survivors. The game-based learning programs could be applied effectively to survivorship care as a new modality of patient education.

Trial registration

This study was retrospectively registered in UMIN-CTR (UMIN000043603) on March 12, 2021.
LncRNA CALML3-AS1 suppresses papillary thyroid cancer progression via sponging miR-20a-5p/RBM38 axis
Authors: Zhang Xiaozhou , Zhang Xiaojian , Jia Qian , Li Hongqiang , Ma Runsheng , Yang Guang , Yin Fengyan , Jiang Nannan , Yin Detao
Published: March 2022

Background

The incidence and mortality of thyroid cancer (TC) has been steadily rising in the past decades. It is imperative to have a better understanding of the molecular mechanisms underlying TC development and identify novel therapeutic targets. This study characterized the role of lncRNA CALML3-AS1 (CALML3-AS1) in the development of papillary thyroid cancer (PTC).

Method

Related mRNAs expression were validated in the tumor and adjacent normal tissues from 52 PTC patients and PTC cell lines by qRT-PCR. Expression of RBM38 was detected by Western blot. We have also conducted CCK-8 and colony formation assays were used to detect the effect of CALML3-AS1 on cell proliferation, Transwell assay was utilized to evaluate cell migration and invasion, apoptosis detected by flow cytometry assay, RNA pull-down and luciferase assays were performed to validate gene predictions.

Results

The results indicated that the expression of both CALML3A-S1 and RBM38 were significantly downregulated in PTC tissues (p < 0.01), while the expression of miR-20a-5p was increased in PTC (p < 0.01). Functionally, CALML3-AS1 overexpression inhibited PTC cell proliferation in vitro and in vivo. Mechanistically, CALML 3-AS1 sponged miR-20a-5p, which in turn leads to the suppression of RBM38 expression and PTC progression.

Conclusions

CALML3-AS1 functions as a ceRNA for miR-20a-5p in the regulation of the expression of RBM38 in PTC. Higher level of CALML3-AS1 serves as a good prognostic indicator of survival in PTC patients. Targeting CALML3-AS1/ miR-20a-5p/RBM38 axis may represent a novel therapeutic strategy in the treatment of PTC.
Prognostic significance of SNCA and its methylation in bladder cancer
Authors: Wu Zhengcun , Xia Chengxing , Zhang Chao , Yang Delin , Ma Kaili
Published: March 2022

Background

The epidemiological investigation of different cancer types in the global population has reported a decreased risk of bladder cancer (BLCA) in Parkinson’s diseases (PD). SNCA a critical gene in PD pathology have been reported involved in tumorigenesis recently. However, the role of SNCA in BLCA remains unclear. This study aimed to explore the potential value of SNCA as a prognostic diagnostic molecular biomarker in BLCA.

Methods

In this study, we explored the expression pattern, prognostic value and promoter methylation level of SNCA in BLCA by GEPIA2, UALCAN, TCGA, GENT2, GEO and c-BioPortal database. Then, we used LinkedOmics database to obtain the co-expression genes of SNCA for further study by WGCNA. We further investigated the correlations between SNCA expression and six main types of immune cell infiltrations and immune signatures by TIMER. Finally, BLCA cell lines treated with 5-Aza-CdR were used to explore the correlation between increased methylation and downregulated mRNA expression.

Results

SNCA was downregulated in tumor tissues in TCGA-BLCA, GENT2 and GEO, which was validated in our cohort by qRT-PCR and immunohistochemistry. SNCA was confirmed as an independent predictor of poor overall survival (OS). LinkedOmics analysis suggested that SNCA regulates cell adhesion molecules, cytokine–cytokine receptor interaction, and complement and coagulation cascades. Twenty-two co-expression gene modules were constructed by WGCNA, and most of them were significantly associated with OS and disease-free survival (DFS). Six key genes (CNTN1, DACT3, MYLK1, PDE2A, RBM24, and ST6GALNAC3) screened also significantly correlated with prognosis. There were significant correlations between SNCA expression and immune infiltrations, especially T cell, suggesting that immune infiltration was one of the reasons for the influence of SNCA on prognosis in BLCA. Analysis by ULACAN and c-BioPortal showed that the promoter methylation of SNCA negatively correlated with its mRNA level. Furthermore, BLCA cell treatment with 5-Aza-CdR revealed that SNCA expression levels were upregulated with decreased methylation.

Conclusion

Our research showed that SNCA was downregulated in BLCA and negatively correlation with DNA methylation. High SNCA expression was confirmed as an independent risk for prognosis. SNCA probably plays an important role in the infiltration of immune cells, especially with T cells. Thus, SNCA may be a promising prognostic biomarker in BLCA patients.
Mortuary and hospital-based HIV mortality surveillance among decedents in a low-resource setting: lessons from Western Kenya
Authors: Nyakeriga Emmanuel , Waruiru Wanjiru , Opollo Valarie , Waruru Anthony , Kingwara Leonard , Onyango Dickens , Junghae Muthoni , Muuo Sheru , Macharia Teresia , Ngugi Catherine , Mwangome Mary , Ali Hammad
Published: March 2022

Background

Lack of dependable morbidity and mortality data complicates efforts to measure the demographic or population-level impact of the global HIV/AIDS epidemic. Mortuary-based mortality surveillance can address gaps in vital statistics in low-resource settings by improving accuracy of measuring HIV-associated mortality and indicators of access to treatment services among decedents. This paper describes the process and considerations taken in conducting mortuary and hospital-based HIV mortality surveillance among decedents in Kenya.

Main text

We conducted HIV mortuary and hospital-based mortality surveillance at two of the largest mortuaries in Kisumu County, Kenya (April 16–July 12, 2019). Medical charts were reviewed for documentation of HIV status among eligible decedents. HIV testing was done on blood and oral fluid samples from decedents with undocumented HIV status and those whose medical records indicated HIV-negative test results > 3 months before death. A panel of experts established the cause of death according to the International Classification of Diseases, 10th Revision rules. Civil registry data for the year 2017 were abstracted and coded to corresponding ICD-10 codes.

Of the 1004 decedents admitted to the two mortuaries during the study period, 49 (4.9%) were unavailable because they had been transferred to other facilities or dispatched for burial before enrolment. Of the 955 available decedents, 104 (10.9%) were ineligible for the study. Blood samples were collected from 659 (77.4%) decedents, and 654 (99.2%) were tested for HIV. Of the 564 decedents eligible for the OraQuick® validation sub-study, 154 were eligible for oral sample collection, and 132 (85.7%) matched pre- and post-embalming oral samples were collected and tested. Of the 851 eligible decedents, 241 (28.3%) had evidence of HIV infection: 119 had a diagnosis of HIV infection recorded in their patient files, and 122 had serological evidence of HIV infection.

Conclusion

This study shows that in low-resource settings, conducting hospital and mortuary-based surveillance is feasible and can be an alternative source of mortality data when civil registry data are inadequate.
Measuring self-care in the general adult population: development and psychometric testing of the Self-Care Inventory
Authors: Luciani Michela , De Maria Maddalena , Page Shayleigh Dickson , Barbaranelli Claudio , Ausili Davide , Riegel Barbara
Published: March 2022

Background

Self-care is important at all stages of life and health status to promote well-being, prevent disease, and improve health outcomes. Currently, there is a need to better conceptualize self-care in the general adult population and provide an instrument to measure self-care in this group. Therefore, the aim of this study was to develop and evaluate the Self-Care Inventory (SCI), a theory-based instrument to measure self-care in the general adult population.

Methods

Based on the Middle Range Theory of Self-Care, the 20-item SCI was developed with three scales: Self-Care Maintenance (8 items), Self-Care Monitoring (6 items), and Self-Care Management (6 items). A cross sectional study with a US-based sample (n = 294) was conducted to test the SCI. Internal validity was assessed with Confirmatory Factor Analysis. Internal consistency reliability was assessed with Cronbach alpha for unidimensional scales or composite reliability and the global reliability index for multidimensional scales. Construct validity was investigated with Pearson correlation to test the relationship between general self-efficacy, positivity, stress, and self-care scores.

Results

The Self-Care Maintenance and Management scales were multidimensional and the Self-Care Monitoring scale was unidimensional. The global reliability index for multidimensional scales was 0.85 (self-care maintenance) and 0.88 (self-care management). Cronbach alpha coefficient of the self-care monitoring scale was 0.88. Test-retest reliability was 0.81 (self-care maintenance), 0.91 (self-care monitoring), and 0.76 (self-care management). The General Self-Efficacy Scale was positively related to all three self-care scale scores: self-care maintenance r = 0.46, p < 0. 001, self-care monitoring r = 0.31, p < 0. 001, and self-care management r = 0.32, p < 0. 001. The positivity score was positively related to self-care maintenance (r = 0.42, p < 0. 001), self-care monitoring (r = 0.29, p < 0. 001), and self-care management (r = 0.34, p < 0. 001) scores. The perceived stress was positively related to the self-care management (r = 0.20, p < 0. 001) score.

Conclusions

The SCI is a theoretically based instrument designed to measure self-care in the general adult population. Preliminary evidence of validity and reliability supports its use in the general adult population.
HIV self-testing implementation, distribution and use among female sex workers in Cotonou, Benin: a qualitative evaluation of acceptability and feasibility
Authors: Boisvert Moreau Marianne , Kintin Frédéric D. , Atchekpe Septime , Batona Georges , Béhanzin Luc , Guédou Fernand A. , Gagnon Marie-Pierre , Alary Michel
Published: March 2022

Background

In Benin, the burden of HIV is disproportionately high among female sex workers (FSWs). HIV testing and knowledge of status are starting points for HIV treatment and prevention interventions. Despite the importance given to testing services in HIV control, its uptake among FSWs remains suboptimal in Benin. HIV self-testing (HIVST) may be useful for increasing testing rates in FSWs.

Methods

We conducted a pilot study of the distribution of saliva-based HIVST among FSWs in Cotonou and its surroundings, Benin. The HIVST promotion and distribution model included three complementary strategies: community-based, facility-based and secondary distribution. In this qualitative study, we explored the elements influencing HIVST implementation, distribution and use among FSWs. We assessed HIVST acceptability and feasibility in this population. We conducted 29 semi-structured individual interviews with FSWs. Data were interpreted with a thematic analysis method, using the Theoretical Domains Framework.

Results

Only two FSWs (6.9%) were aware of HIVST before participating in the study. All participants were interested in using HIVST if available in Benin. Many advantages of HIVST were mentioned, including: autonomy, privacy, accessibility, time saving, and the fact that it is a painless test. Barriers to the use of HIVST included: the fear of unreliability, the lack of psychological support and medical follow-up and the possibility of result dissimulation. Participants thought HIVST was easy to use without assistance. HIVST enabled linkage to care for a few FSWs in denial of their HIV-positive status. No case of suicide or violence associated with HIVST was reported. HIVST secondary distribution within FSWs social network was well received. FSWs’ boyfriends and clients showed interest in using the device. Some FSWs reported using HIVST to practice serosorting or to guide their decisions regarding condom use.

Conclusions

Our study shows a very high level of acceptability for HIVST among FSWs in Cotonou and its surroundings. Results also demonstrate the feasibility of implementing HIVST distribution in Benin. HIVST should be implemented in Benin quickly and free of charge for all individuals at risk of HIV. HIVST offer should be integrated with comprehensive sexual health and prevention services.
Distal insertion rupture of lateral ankle ligament as a predictor of weakened and delayed sports recovery after acute ligament repair: mid-term outcomes of 117 cases
Authors: Du Mingze , Li Jun , Jiao Chen , Guo Qinwei , Hu Yuelin , Jiang Dong
Published: March 2022

Background

For lateral ankle ligament rupture, surgical repair has been considered for patients requiring return to high-demanding sports. However, there is a lack of systematic research regarding arthroscopic treatment followed by ligament repair for severe acute ankle sprain. The purpose of this study was to analyze the mid-term outcomes of arthroscopy followed by open anatomic lateral ankle ligament repair surgery for acute lateral ankle sprain and the impact of ligament rupture site on the outcomes.

Methods

Professional or amateur athletes with clinically- and radiologically-confirmed grade III acute lateral ankle ligament injuries undergoing ankle arthroscopy followed by open anatomic ligament repair between June 2007 and May 2017 were reviewed. Intra-articular lesions and the location of rupture were first examined under arthroscopy. Simple suture repair was performed for mid- substance ligament rupture (middle group), while suture repair with anchors were used for the ruptures near the ligament attachment site on the fibular (proximal group), talar or the calcaneal side (distal group). Outcomes were evaluated at final follow-up, including visual analog scale (VAS) pain score, American Orthopaedic Foot & Ankle Society (AOFAS) score, Tegner score, time to return to sports, resumption of pre-injury sports level, sprain recurrence and range of motion (ROM).

Results

A total of 117 patients were included for analysis, with a mean follow-up duration of 46.4 ± 16.1 months. There were 48 (41%) cases in the proximal group, 41 (35%) cases in the middle group and 28 (24%) cases in the distal group respectively. At final follow-up, all of the VAS score, AOFAS score and the Tegner score were significantly improved from the pre-operative level (p < 0.001). 12 (10%) patients complained of sprain recurrence during follow-up. 14 (12%) patients reported mild ROM restriction and 7 (6%) patients experienced transient skin numbness. The average time to return to pre-injury sports was 4.34 ± 1.11 months. The smallest proportion (86% ± 13%) of resumption of pre-injury sports level was reported from the distal group, compared with 93% ± 12% for the proximal group and 89% ± 14% for the middle group (p = 0.037). Time to return to sports was significantly longer for the distal group, with an average of 4.59 ± 1.27 months compared to 3.99 ± 1.09 months for the proximal group and 4.58 ± 0.90 months for the middle group (p = 0.009).

Conclusions

Ankle arthroscopy followed by open anatomic ligament repair is a reliable procedure for patients requiring return to high demanding sports after severe acute ankle sprains. Distal rupture near the talar or calcaneal end was associated with delayed return-to-sport and inferior performance in resuming pre-injury sports level.
A new modified Duckett urethroplasty for repair of proximal hypospadias with severe chordee: outcomes of 133 patients
Authors: Wang Chong , Zhang Zhi-Cheng , Zhang De-Ying , Hua Yi , Liu Feng , He Da-Wei , Wei Guang-Hui , Liu Xing
Published: March 2022

Background

Despite the continuous development and evolution of surgical methods and techniques, proximal hypospadias remains one of the most challenging issues for pediatric urologists. This study aims to evaluate the indications and postoperative complications of our new modified Duckett urethroplasty.

Methods

A total of 133 patients with proximal hypospadias who underwent repair of the modified Duckett urethroplasty from February 2016 to February 2021 were reviewed. The median age of patients was 3 years (range 1–16). All patients had severe chordee. One senior experienced pediatric urologist performed all the surgeries. Catheter was removed 14 days after the surgery.

Results

The location of the urethral meatus was proximal penile in 26 patients (19.5%), penoscrotal in 60 (45.1%), scrotal in 31 (23.3%), and perineal in 16 (12.0%). The mean length of the urethral defect was 4.5 cm (range 2.5–10). The median duration of follow-up was 46 months (range 8–67). Complications occurred in 31 patients (23.3%), including urethra-cutaneous fistula in 22 (16.5%), urethral stenosis in 7 (5.3%), and urethral diverticulum in 2 (1.5%). No recurrent chordee were found in all cases. All patients who developed complications were treated successfully at our hospital.

Conclusions

Our modified Duckett urethroplasty showed functionally and cosmetically favorable outcomes, with a lower incidence of postoperative complications. To the best of our knowledge, the novel Duckett technique is a feasible and suitable option for patients who suffer from proximal hypospadias with severe chordee and dysplasia of the urethral plate.
An exploration of primary care healthcare professionals’ understanding of pain and pain management following a brief pain science education
Authors: Mankelow Jagjit , Ryan Cormac G. , Green Paul W. , Taylor Paul C. , Martin Denis
Published: March 2022

Background

Persistent pain is a leading cause of disability worldwide yet implementation of clinical guidelines that recommend a biopsychosocial approach remains a challenge in clinical practise. Limited pain understanding amongst clinicians may be partly responsible for this.

Purpose of the study

1) Qualitatively explore the experience of receiving PSE, understanding of PSE and operationalisation of PSE-related principles in routine clinical practice. 2) Quantitatively explore pain knowledge, attitudes, and behaviours of general practitioners (GPs) and nurse practitioners (NPs) before and after pain science education (PSE).

Methods

An exploratory, single-site, mixed-methods study in north-east England. Fifteen NPs/GPs completed questionnaires and a case-vignette before and after a 70-min face-to-face PSE lecture. Qualitative data were thematically analysed from two focus groups after the intervention.

Results

Clinicians’ relatively high prior levels of knowledge, attitudes, and behaviour were similar after PSE. Qualitative themes described facilitation of self-reflection on pain management behaviours, and difficulties in operationalising PSE principles in practise including: limited patient rapport; short appointment times; patients’ passive and often oppositional biomedical treatment expectations; and clinicians’ lack of readily understandable language to communicate with patients.

Conclusion

The findings highlight the value of PSE perceived by these clinicians who were already favourably inclined towards biopsychosocial pain management. They sought more resources for their personal learning and for communication with patients. Even with such favourable disposition, the practicalities and environment of clinical practice impeded the operationalisation of PSE-related principles.

Trial registration

This study was prospectively registered at ClinicalTrials.Gov (NCT04587596) in October 2020.
Tailoring an online breastfeeding course for Southeast Asian paediatric trainees- A qualitative study of user experience from Malaysia and Thailand
Authors: Lee Yew Kong , Wattanapisit Apichai , Ng Chirk Jenn , Boey Christopher Chiong Meng , Ahmad Kamar Azanna , Choo Yao Mun , Hong Joyce Soo Synn , Cheah Fook Choe , Tang Swee Fong , Poh Bee Koon , Chongviriyaphan Nalinee , Siwarom Sirinapa , Visuthranukul Chonnikant , Koletzko Berthold
Published: March 2022

Background

This study explored the user experiences of paediatric postgraduate trainees in Malaysia and Thailand in using a 2 h and 15 min online module for breastfeeding developed for Southeast Asia, which was adapted from existing European online modules for European and German Continuing Medical Education (CME) credits.

Methods

A qualitative study using focus group discussions (FGDs) was conducted with paediatric postgraduate trainees who used an online English-language breastfeeding module in two Thai universities (May 2020, done online) and two Malaysian universities (Sept- Nov 2019, in-person). FGDs explored module usability and utility. Sessions were transcribed verbatim and analysed thematically. The process of coding was done collaboratively by Thai and Malaysian researchers.

Results

Twenty Six resident trainees participated (Thai, n = 13; Malaysian, n = 13). Ages ranged from 29–34 years old, with 21 females. Nineteen participants had never used online learning modules prior to this. Participants took between 1 to 5 sessions to complete the breastfeeding module. Four themes emerged from their experience. 1) The online learning module was more engaging and detailed than previous lectures, courses and/or books, but lacked hands-on training. 2) Using an online platform facilitated learning as eased navigation and resource searching, however, problems were encountered navigating the module on some devices. 3) Learners preferred less words and more graphics, as this helped them capture key messages. 4) Regionally tailored content elicited a mixed reaction from participants.

Conclusions

Users found that the adapted module compared favourably with previous learning experiences. However, online learning modules lack hands-on training, and implementation should ideally incorporate a mix of both. Consideration of device diversity and preferences for how content was adapted for local settings are needed for tailoring.
Collection and use of human materials during TB clinical research; a review of practices
Authors: Ochieng Joseph , Kwagala Betty , Sewankambo Nelson
Published: March 2022

Background

Human biological materials are usually stored for possible future use in research because they preserve valuable biological information, save time and resources, which would have been spent on collection of fresh samples. However, use of these materials may pose ethical challenges such as unauthorized disclosure of genetic information, which can result in dire consequences for individuals or communities including discrimination, stigma, and psychological harm; has biosecurity implications; and loss of control or ownership of samples or data. To understand these problems better, we evaluated the extent to which tuberculosis (TB) clinical research protocols that were used to collect and store biological materials for future use conform to the requirements stated in the Uganda national guidelines for research involving humans as participants.

Methods

This was a retrospective review of TB clinical research projects approved by the Uganda National Council for Science and Technology (UNCST) from 2011 to 2015, to examine whether they fulfilled the requirements for ethical collection and use of human materials. Data were abstracted through review of the project protocols using a template developed based on the informed consent and the Materials Transfer Agreement (MTA) requirements in the national guidelines.

Results

Out of 55 research protocols reviewed, most of the protocols 83.6% had been used to collect the stored samples (sputum, blood and sometimes urine), 28% had a section on specimen collection and 24% mentioned ownership of the biological materials. With respect to review of the consent forms used in the studies that stored materials for future use, only 9% of the protocols had a separate consent form for storage of materials, 4.5% of the consent forms explained the risks, 11.4% explained the purpose of the study while 6.8% mentioned the place of storage for the collected materials.

Conclusion

Many of the studies reviewed did not meet the requirements for collection and storage of biological materials contained in the national guidelines, which indicates a need to additional training on this topic.
The repertoire of testicular extracellular vesicle cargoes and their involvement in inter-compartmental communication associated with spermatogenesis
Authors: Choy Kathleen Hoi Kei , Chan Sze Yan , Lam William , Jin Jing , Zheng Tingting , Law Tin Yu Samuel , Yu Sidney Siubun , Wang Weiping , Li Linxian , Xie Gangcai , Yim Howard Chi Ho , Chen Hao , Fok Ellis Kin Lam
Published: March 2022

Background

Spermatogenesis is regulated by a complex network of intercellular communication processes. Extracellular vesicles (EVs) are one of the important mediators in intercellular communication. Previous reports have demonstrated the involvement of EVs from the epididymis and prostate in sperm maturation and function. However, the presence of EVs in the testis and their potential involvement in spermatogenesis has not been explored. Here, we have established a testis dissociation protocol that allows the isolation and characterization of testicular EVs.

Results

We show that testicular EVs are specifically and efficiently taken up by somatic cells and germ cells, including the spermatozoa in the interstitial space and the seminiferous tubule compartments. We profiled the proteome of testicular EVs and probed the cell types that release them, revealing the potential contributions from the Leydig cells and testicular macrophages. Moreover, we sequenced the small RNA cargoes of testicular EVs and identified sets of small non-coding RNAs that were overlooked in the testis transcriptome. Selected miRNA candidates in testicular EVs were found in sperm RNA payload and demonstrated specific resistance towards ribonuclease A independent of the vesicle membrane. Small molecule inhibition of EV secretion perturbed spermatogenesis via inter-compartmental communication.

Conclusions

Together, our study provides a valuable resource on the repertoire of cargoes carried by testicular EVs and uncovers a physiological function of testicular EVs in inter-compartmental communication associated to spermatogenesis.
Diabetic kidney disease and risk of incident stroke among adults with type 2 diabetes
Authors: Kaze Arnaud D. , Jaar Bernard G. , Fonarow Gregg C. , Echouffo-Tcheugui Justin B.
Published: March 2022

Background

Data on the relations between kidney function abnormalities and stroke in type 2 diabetes are limited. We evaluated the associations of kidney function abnormalities and chronic kidney disease (CKD) stages with incident stroke in a large sample of adults with type 2 diabetes.

Methods

Participants with type 2 diabetes from the Action to Control Cardiovascular Risk in Diabetes (ACCORD) study without history of stroke at baseline were included. Urine albumin-to-creatinine ratio (UACR) and estimated glomerular filtration rate (eGFR) were assessed at baseline. CKD categories were defined according to the KDIGO (Kidney Disease: Improving Global Outcomes) guidelines. Cox proportional hazards regression models were used to compute hazard ratios (HR) and 95% confidence intervals (CI) for stroke in relation to measures of kidney function and CKD categories.

Results

A total of 9170 participants (mean age 62.8 [SD: 6.6] years, 38.2% women, 62.9% white) were included. Over a median follow-up of 4.9 years (interquartile range: 4.0–5.7), 156 participants developed a stroke (incidence rate 3.6/1000 person-years [95% CI 3.0–4.2]). After adjusting for relevant confounders, higher UACR and lower eGFR were each associated with increased risk of stroke. Compared to UACR < 30 mg/g, moderate albuminuria and severe albuminuria were associated with increasing hazards for stroke (HR 1.61 [95% CI 1.12–2.32] and 2.29 [95% CI 1.39–3.80], respectively). Compared to eGFR of ≥ 60 mL/min/1.73 m2, decreased eGFR (eGFR < 60 mL/min/1.73 m2) was associated with higher risk of stroke (HR 1.50, 95% CI 0.98–2.29). Compared to no CKD, worsening CKD stage was associated with an increasing risk of stroke (HRs of 1.76 [95% CI 1.10–2.83] for CKD G1, 1.77 [95% CI 1.13–2.75] for CKD G2, and 2.03 [95% CI 1.27–3.24] for CKD G3).

Conclusions

In a large sample of adults with type 2 diabetes, increasing albuminuria and worsening stages of early CKD were independently associated with higher risk of incident stroke.

Trial registration

ClinicalTrials.gov. Identifier: NCT00000620.
Chimeric virus-like particles presenting tumour-associated MUC1 epitope result in high titers of specific IgG antibodies in the presence of squalene oil-in-water adjuvant: towards safe cancer immunotherapy
Authors: Panasiuk Mirosława , Zimmer Karolina , Czarnota Anna , Narajczyk Magdalena , Peszyńska-Sularz Grażyna , Chraniuk Milena , Hovhannisyan Lilit , Żołędowska Sabina , Nidzworski Dawid , Żaczek Anna J. , Gromadzka Beata
Published: March 2022

Background

Immunotherapy is emerging as a powerful treatment approach for several types of cancers. Modulating the immune system to specifically target cancer cells while sparing healthy cells, is a very promising approach for safer therapies and increased survival of cancer patients. Tumour-associated antigens are favorable targets for cancer immunotherapy, as they are exclusively expressed by the cancer cells, minimizing the risk of an autoimmune reaction. The ability to initiate the activation of the immune system can be achieved by virus-like particles (VLPs) which are safe and potent delivery tools. VLP‐based vaccines have evolved dramatically over the last few decades and showed great potential in preventing infectious diseases. Immunogenic potency of engineered VLPs as a platform for the development of effective therapeutic cancer vaccines has been studied extensively. This study involves recombinant VLPs presenting multiple copies of tumour-specific mucin 1 (MUC1) epitope as a potentially powerful tool for future immunotherapy.

Results

In this report VLPs based on the structural protein of Norovirus (NoV VP1) were genetically modified to present multiple copies of tumour-specific MUC1 epitope on their surface. Chimeric MUC1 particles were produced in the eukaryotic Leishmania tarentolae expression system and used in combination with squalene oil-in-water emulsion MF59 adjuvant to immunize BALB/c mice. Sera from vaccinated mice demonstrated high titers of IgG and IgM antibodies which were specifically recognizing MUC1 antigen.

Conclusions

The obtained results show that immunization with recombinant chimeric NoV VP1- MUC1 VLPs result in high titers of MUC1 specific IgG antibodies and show great therapeutic potential as a platform to present tumour-associated antigens.

Graphical Abstract
Comparative efficacy of bio-selenium nanoparticles and sodium selenite on morpho-physiochemical attributes under normal and salt stress conditions, besides selenium detoxification pathways in Brassica napus L.
Authors: El-Badri Ali Mahmoud , Hashem Ahmed M. , Batool Maria , Sherif Ahmed , Nishawy Elsayed , Ayaad Mohammed , Hassan Hamada M. , Elrewainy Ibrahim M. , Wang Jing , Kuai Jie , Wang Bo , Zheng Shixue , Zhou Guangsheng
Published: March 2022

Selenium nanoparticles (SeNPs) have attracted considerable attention globally due to their significant potential for alleviating abiotic stresses in plants. Accordingly, further research has been conducted to develop nanoparticles using chemical ways. However, our knowledge about the potential benefit or phytotoxicity of bioSeNPs in rapeseed is still unclear. Herein, we investigated the effect of bioSeNPs on growth and physiochemical attributes, and selenium detoxification pathways compared to sodium selenite (Se (IV)) during the early seedling stage under normal and salt stress conditions. Our findings showed that the range between optimal and toxic levels of bioSeNPs was wider than Se (IV), which increased the plant’s ability to reduce salinity-induced oxidative stress. BioSeNPs improved the phenotypic characteristics of rapeseed seedlings without the sign of toxicity, markedly elevated germination, growth, photosynthetic efficiency and osmolyte accumulation versus Se (IV) under normal and salt stress conditions. In addition to modulation of Na+ and K+ uptake, bioSeNPs minimized the ROS level and MDA content by activating the antioxidant enzymes engaged in ROS detoxification by regulating these enzyme-related genes expression patterns. Importantly, the main effect of bioSeNPs and Se (IV) on plant growth appeared to be correlated with the change in the expression levels of Se-related genes. Our qRT-PCR results revealed that the genes involved in Se detoxification in root tissue were upregulated upon Se (IV) treated seedlings compared to NPs, indicating that bioSeNPs have a slightly toxic effect under higher concentrations. Furthermore, bioSeNPs might improve lateral root production by increasing the expression level of LBD16. Taken together, transamination and selenation were more functional methods of Se detoxification and proposed different degradation pathways that synthesized malformed or deformed selenoproteins, which provided essential mechanisms to increase Se tolerance at higher concentrations in rapeseed seedlings. Current findings could add more knowledge regarding the mechanisms underlying bioSeNPs induced plant growth.

Graphical Abstract
Hydroxychloroquine attenuates neuroinflammation following traumatic brain injury by regulating the TLR4/NF-κB signaling pathway
Authors: Hu Jian , Wang Xue , Chen Xiongjian , Fang Yani , Chen Kun , Peng Wenshuo , Wang Zhengyi , Guo Kaiming , Tan Xianxi , Liang Fei , Lin Li , Xiong Ye
Published: March 2022

Background

After traumatic brain injury (TBI), an acute, robust inflammatory cascade occurs that is characterized by the activation of resident cells such as microglia, the migration and recruitment of peripheral immune cells and the release of inflammatory mediators that induce secondary cell death and impede neurological recovery. In addition, neuroinflammation can alter blood–brain barrier (BBB) permeability. Controlling inflammatory responses is considered a promising therapeutic approach for TBI. Hydroxychloroquine (HCQ) has already been used clinically for decades, and it is still widely used to treat various autoimmune diseases. However, the effects of HCQ on inflammation and the potential mechanism after TBI remain to be defined. The aim of the current study was to elucidate whether HCQ could improve the neurological recovery of mice post-TBI by inhibiting the inflammatory response via the TLR4/NF-κB signaling pathway.

Methods

C57BL/6 mice were subjected to controlled cortical impact (CCI) and randomly divided into groups that received intraperitoneal HCQ or vehicle daily after TBI. TAK-242 (3.0 mg/kg), an exogenous TLR4 antagonist, was injected intraperitoneally 1 h before TBI. Behavioral assessments were performed on days 1 and 3 post-TBI, and the gene expression levels of inflammatory cytokines were analyzed by qRT-PCR. The presence of infiltrated immune cells was examined by flow cytometry and immunostaining. In addition, BBB permeability, tight junction expression and brain edema were investigated.

Results

HCQ administration significantly ameliorated TBI-induced neurological deficits. HCQ alleviated neuroinflammation, the activation and accumulation of microglia and immune cell infiltration in the brain, attenuated BBB disruption and brain edema, and upregulated tight junction expression. Combined administration of HCQ and TAK-242 did not enhance the neuroprotective effects of HCQ.

Conclusions

HCQ reduced proinflammatory cytokine expression, and the underlying mechanism may involve suppressing the TLR4/NF-κB signaling pathway, suggesting that HCQ is a potential therapeutic agent for TBI treatment.
Integrative analyses of genes related to femoral head osteonecrosis: an umbrella review of systematic reviews and meta-analyses of observational studies
Authors: Lee Sangyeob , Yoo Jun-Il , Kang Yang-Jae
Published: March 2022

Background

Femoral head osteonecrosis (FHON) is a worldwide challenging clinical topic. Steroid use is one of the main etiologies of FHON. There are several genetic variants associated with FHON. Therefore, the purpose of this umbrella review was to provide a comprehensive summary of a meta-analysis and systematic review of genetic variations associated with nonsteroidal and steroid-induced FHON.

Methods

The eligible studies were selected from the PubMed and MEDLINE databases for the collection of diverse systematic meta-analyses and reviews. The genetic main effect score was assigned using the Human Genome Epidemiology Network’s Venice criteria to assess the cumulative evidence on the effects of a single nucleotide polymorphism (SNP) on FHON.

Results

Eight articles reported the meta-analysis of candidate SNP-based studies covering eight genes and 13 genetic variants. In the nonsteroid-induced FHON genetic variants including rs2012390 and rs11225394 in MMP8, rs1800629 and rs361525 in tumor necrosis factor (TNF)-α, VNTR in intron 4, rs1799983 and rs2070744 in endothelial nitric oxide synthase (eNOS), rs2010963 in vascular endothelial growth factor (VEGF), and rs6025 in factor V showed significance in each reference. The steroid-induced FHON genetic variants including rs693 and rs1042031 in apolipoprotein (Apo)B, rs1045642 in ABCB1, and rs1799889 in PAI-1 showed significance in each reference.

Conclusion

Based on the systematic review conducted in this study, we organized the genomes associated with FHON and looked at each contribution. Our results could give an integrative approach for understanding the mechanism of FHON etiology. It is expected that these results could contribute to the strategy of prediagnosis, evaluating the individual risk of nonsteroid-induced and steroid-induced FHON.

Level of Evidence: Level I.
Postpartum depression in maternal thyroidal changes
Authors: Schmidt Paula Michele da Silva , Longoni Aline , Pinheiro Ricardo Tavares , Assis Adriano Martimbianco de
Published: March 2022

Evidence in the literature has suggested that there may be an association between thyroid antibodies and depression during pregnancy and in the postpartum period. Thus, this study aims to conduct a systematic review on the prevalence of postpartum depression (PPD) in women with thyroid abnormalities during pregnancy or in the postpartum period. For this review, we used four databases (PubMed, Lilacs, Scielo, and Scopus). Fifteen studies were selected; one study used a case–control design, four used a cross-sectional design and ten utilized prospective cohort designs. All studies were restricted to up to 1 year postpartum, and 46.7% focused on a period between immediate postpartum and 6 months postpartum. Estimates of the prevalence of PPD in pregnant women with thyroid disorders ranged between 8.3% and 36.0%. For follow-up studies, the cumulative incidence of self-reported depression from the primary episode in the first postpartum year was 6.3% in a high-city survey. Although some authors consider the status of positive anti-TPO antibodies to be a possible marker of vulnerability to depression , it is not yet possible to conclude whether thyroid function in the pregnancy-puerperal cycle is involved with the development of PPD.
Non-medical factors in prehospital resuscitation decision-making: a mixed-methods systematic review
Authors: Milling Louise , Kjær Jeannett , Binderup Lars Grassmé , de Muckadell Caroline Schaffalitzky , Havshøj Ulrik , Christensen Helle Collatz , Christensen Erika Frischknecht , Lassen Annmarie Touborg , Mikkelsen Søren , Nielsen Dorthe
Published: March 2022

Aim

This systematic review explored how non-medical factors influence the prehospital resuscitation providers’ decisions whether or not to resuscitate adult patients with cardiac arrest.

Methods

We conducted a mixed-methods systematic review with a narrative synthesis and searched for original quantitative, qualitative, and mixed-methods studies on non-medical factors influencing resuscitation of out-of-hospital cardiac arrest. Mixed-method reviews combine qualitative, quantitative, and mixed-method studies to answer complex multidisciplinary questions. Our inclusion criteria were peer-reviewed empirical-based studies concerning decision-making in prehospital resuscitation of adults > 18 years combined with non-medical factors. We excluded commentaries, case reports, editorials, and systematic reviews. After screening and full-text review, we undertook a sequential exploratory synthesis of the included studies, where qualitative data were synthesised first followed by a synthesis of the quantitative findings.

Results

We screened 15,693 studies, reviewed 163 full-text studies, and included 27 papers (12 qualitative, two mixed-method, and 13 quantitative papers). We identified five main themes and 13 subthemes related to decision-making in prehospital resuscitation. Especially the patient’s characteristics and the ethical aspects were included in decisions concerning resuscitation. The wishes and emotions of bystanders further influenced the decision-making. The prehospital resuscitation providers’ characteristics, experiences, emotions, values, and team interactions affected decision-making, as did external factors such as the emergency medical service system and the work environment, the legislation, and the cardiac arrest setting. Lastly, prehospital resuscitation providers’ had to navigate conflicts between jurisdiction and guidelines, and conflicting values and interests.

Conclusions

Our findings underline the complexity in prehospital resuscitation decision-making and highlight the need for further research on non-medical factors in out-of-hospital cardiac arrest.