bluuebunny/crossref_metadata_2025 huggingface dataset:
A Qualitative Study of the Impact of the COVID-19 Pandemic on a Sample of Patients With Chronic Pain
Authors: Mohamed Ali Ola , Borg Debono Victoria , Anthonypillai Jennifer , Hapidou Eleni G.
Published: April 2022

This qualitative phenomenological study examined the impact of the COVID-19 pandemic on the lives of patients living with chronic pain. Patients referred to an intensive interdisciplinary pain management program between June 2020 to June 2021 were asked, “How did the COVID-19 pandemic affect your life?” as part of their interdisciplinary assessment. Ninety patients (50 Veterans, 40 civilians) provided comments to this question, which were independently organized into themes using an inductive approach by 4 researchers. Nine main themes emerged: (1) changed psychological state, (2) minimal to no effect, (3) affected personal life activities, (4) changes in accessing care, (5) changes in work/education situation, (6) changes in family dynamics, (7) experiencing more annoyances, (8) COVID-19 pandemic is a barrier to making positive changes, and (9) got COVID-19. Themes are consistent with topics of interest in light of this ongoing, global stressor. Most commonly reported themes reflected changes in psychological well-being and changes in access to care, highlighting similarities between life with chronic pain and life under the pandemic for this group.
Perceived Physician Empathy in Pediatric Orthopedics: A Cross-Sectional Study
Authors: Singleton Ian M , Garfinkel Rachel J , Malone Jason B , Temkit M’Hamed H , Belthur Mohan V
Published: April 2022

Empathy is the cornerstone of the patient–physician relationship and is consistently ranked by patients as one of the most important factors in the quality of their care. In this paper we examine the degree to which perceived physician empathy is associated with the characteristics of the caregiver (parent or legal guardian) and physician in pediatric orthopedic surgery. This was a cross-sectional survey study of 200 English-speaking caregivers of pediatric patients at a large children's hospital. The Consultation and Relational Empathy (CARE) Measure was used to measure perceived physician empathy. Only if the caregiver felt carefully listened to by the physician ( p-value < 0.001), and if the physician showed respect for what the caregiver had to say ( p-value = 0.007) were statistically significant and positively associated with perceived physician empathy. The most significant determinant of perceived physician empathy is whether the caregiver felt listened to during the encounter. Other factors such as caregiver demographics, health literacy, self-rated mental health, wait time, and time spent with the physician do not significantly affect perceived physician empathy.
Cytokine Storm in COVID 19 Culminating in Candida Endocarditis
Authors: Kaneria Mala Vinod , Budhe Abhijeet , Lade Prasenjit , Poyekar Tejas
Published: April 2022

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), had made its demonic debut on the world stage in December 2019 and has been sweeping across the globe since then. 1 This new kid on the block soon also joined the cluster of risk factors, leading to fungal infections. Cases of mucormycosis, colloquially called “black fungus,” (COVID-19 associated mucormycosis [CAM]), had escalated in India, and the focus then shifted to Candida, the so-called “white fungus.” The dysregulated immune system in COVID-19, along with the immunosuppressants used to treat it, may give rise to fatal secondary infections. We present a patient who had a stormy, prolonged course following COVID-19, with multiple bacterial and viral infections, subsequently culminating in fungal endocarditis with Candida tropicalis.
Bioinformatics analysis reveals immune prognostic markers for overall survival of colorectal cancer patients: a novel machine learning survival predictive system
Authors: Zhang Zhiqiao , Huang Liwen , Li Jing , Wang Peng
Published: April 2022

Objectives

Immune microenvironment was closely related to the occurrence and progression of colorectal cancer (CRC). The objective of the current research was to develop and verify a Machine learning survival predictive system for CRC based on immune gene expression data and machine learning algorithms.

Methods

The current study performed differentially expressed analyses between normal tissues and tumor tissues. Univariate Cox regression was used to screen prognostic markers for CRC. Prognostic immune genes and transcription factors were used to construct an immune-related regulatory network. Three machine learning algorithms were used to create an Machine learning survival predictive system for CRC. Concordance indexes, calibration curves, and Brier scores were used to evaluate the performance of prognostic model.

Results

Twenty immune genes (BCL2L12, FKBP10, XKRX, WFS1, TESC, CCR7, SPACA3, LY6G6C, L1CAM, OSM, EXTL1, LY6D, FCRL5, MYEOV, FOXD1, REG3G, HAPLN1, MAOB, TNFSF11, and AMIGO3) were recognized as independent risk factors for CRC. A prognostic nomogram was developed based on the previous immune genes. Concordance indexes were 0.852, 0.778, and 0.818 for 1-, 3- and 5-year survival. This prognostic model could discriminate high risk patients with poor prognosis from low risk patients with favorable prognosis.

Conclusions

The current study identified twenty prognostic immune genes for CRC patients and constructed an immune-related regulatory network. Based on three machine learning algorithms, the current research provided three individual mortality predictive curves. The Machine learning survival predictive system was available at: https://zhangzhiqiao8.shinyapps.io/Artificial_Intelligence_Survival_Prediction_for_CRC_B1005_1/, which was valuable for individualized treatment decision before surgery.
Implementing a community-based shared care breast cancer survivorship model in Singapore: a qualitative study among primary care practitioners
Authors: Ke Yu , Fok Rose Wai Yee , Soong Yoke Lim , Loh Kiley Wei-Jen , Farid Mohamad , Low Lian Leng , Quah Joanne Hui Min , Vasanwala Farhad Fakhrudin , Low Sher Guan , Soh Ling Ling , Tan Ngiap-Chuan , Chan Alexandre
Published: April 2022

Background

The adaptability of existing recommendations on shared care implementation to Asian settings is unknown. This qualitative study aims to elicit public- and private-sectors primary care practitioners’ (PCPs) perspectives on the sustainable implementation of a shared care model among breast cancer survivors in Singapore.

Methods

Purposive sampling was employed to engage 70 PCPs from SingHealth Polyclinics, National University Polyclinics, National Healthcare Group Polyclinics, and private practice. Eleven focus groups and six in-depth interviews were conducted between June to November 2018. All sessions were audio-recorded and transcribed verbatim. Guided by the RE-AIM framework, we performed deductive thematic analysis in QSR NVivo 12.

Results

PCPs identified low-risk breast cancer survivors who demonstrated clear acceptability of PCPs’ involvement in follow-up as suitable candidates for shared care. Engagement with institution stakeholders as early adopters is crucial with adequate support through PCP training, return pathways to oncologists, and survivorship care plans as communication tools. Implementation considerations differed across practices. Selection of participating PCPs could consider seniority and interest for public and private practice, respectively. Proposed adoption incentives included increased renumeration for private PCPs and work recognition for public PCPs. Public PCPs further proposed integrating shared care elements to their existing family medicine clinics.

Conclusions

PCPs perceived shared care favorably as it echoed principles of primary care to provide holistic and well-coordinated care. Contextual factors should be considered when adapting implementation recommendations to Asian settings like Singapore. With limited competitive pressure, the government is then pivotal in empowering primary care participation in survivorship shared care delivery.
Characteristics of primary signet ring cell carcinoma of colon and rectum: a case control study
Authors: Weng Meng-Tzu , Chao Ko-Han , Tung Chien-Chih , Chang Hao-Chun , Shih I-Lun , Lin Been-Ren , Shieh Ming-Jium , Shun Chia-Tung , Wong Jau-Min , Wei Shu-Chen
Published: April 2022

Background

Primary signet ring cell carcinoma of the colon and rectum (PSRCCR) is rare, usually diagnosed at advanced stage with poor outcomes. We aimed to find possible diagnostic clues in order to help diagnosis.

Methods

A retrospective study of PSRCCR patients from 1993 to 2018 was reviewed at a single tertiary center. Colorectal adenocarcinoma patients as control group with 1:4 ratio was also enrolled.

Results

18 patients with PSRCCR were identified. The prevalence rate was 0.16% (18 of 11,515). The mean age was 50.2 years-old in PSRCCR group and 63 years-old in non-SRCC colorectal cancer patients (p < 0.001). Diagnosis tool depends on colonoscopy were much less in PSRCCR group than control group (44.4% vs 93%, p < 0.001). SRCC patients had higher level of CEA (68.3 vs 17.7 ng/mL, p = 0.004) and lower level of Albumin (3.4 vs 4.3 g/dL, p < 0.001). The majority of PSRCCR tumor configuration was ulcerative and infiltrative. More PSRCCR pathology presented as high-grade carcinoma (66.7 vs 1.4%, p < 0.001) and lymphovascular invasion (77.8 vs 44.4%, p = 0.011) than control group. More PSRCCR patients were diagnosed at advanced stage (88.8 vs 40.3%, p = 0.001). Higher mortality was also noticed in PSRCCR group than control group (72.2 vs 20.8%, p < 0.001).

Conclusion

For young patients with long segment colonic stenosis and ulcerative/ infiltrative mucosa but endoscopic biopsy failed to identify malignant cells, earlier operation or non-colon site biopsy is suggested for diagnosing the PSRCCR.
Study protocol for a modified antenatal care program for pregnant women with a low risk for adverse outcomes—a stepped wedge cluster non-inferiority randomized trial
Authors: Stålberg Valerie , Krevers Barbro , Lingetun Lovisa , Eriksson Therese , Josefsson Ann , Lilliecreutz Caroline
Published: April 2022

Background

It is crucial to provide care based on individual needs. Swedish health care is obliged to give care on equal conditions for the entire population. The person with the greatest need should be given the most care, and the health care system should strive to be cost-efficient. Medical and technical advances have been significant during the last decades and the recent Covid-19 pandemic has caused a shift in health care, from in-person visits to virtual visits. The majority of pregnant women with a low risk assessment have an uncomplicated antenatal course without adverse events. These women probably receive excessive and unnecessary antenatal care. This study will investigate if an antenatal care program for healthy pregnant women with a low risk for adverse outcomes could be safely monitored with fewer in-person visits to a midwife, and with some of them replaced by virtual visits.

Methods

This is a non-inferiority trial where a stepped wedge cluster randomized controlled design will be used. Data collection includes register data and questionnaires that concern antenatal, obstetric and neonatal outcomes, patient- and caregiver-reported experiences, healthcare-economy, and implementation aspects. The modified antenatal care (MAC) study is performed in parts of the southeast of Sweden, which has approximately 8200 childbirths annually. At the start of the study, all antenatal care centers included in the study will use the same standard antenatal care (SAC) program. In the MAC program the in-person visits to a midwife will be reduced to four instead of eight, with two additional virtual meetings compared with the SAC program.

Discussion

This presented study protocol is informed by research knowledge. The protocol is expected to provide a good structure for future studies on changed antenatal care programs that introduce virtual visits for healthy pregnant women with a low risk for adverse outcomes, without risking quality, safety, and increased costs.

Trial registration

The study is registered the 21th of April 2021 in the ISRCTN registry with trial ID: ISRCTN14422582, retrospectively registered.
From the hidden to the obvious: classification of primary and secondary school student suicides using cluster analysis
Authors: Wong Anna , Lai Carmen C. S. , Shum Angie K. Y. , Yip Paul S. F.
Published: April 2022

Background

Suicide is one of the leading causes of death in children and youth. Using a sample of fatal suicides among school-aged students in Hong Kong, this study aimed to demonstrate how the classification of children and adolescent suicides into distinct subgroups using cluster analysis can alert us to the heterogeneous nature of the student suicide population and increase our understanding of multidimensional underlying causes. 

Methods

Deaths by suicide of Hong Kong primary and secondary school students occurring between 2013–16 were identified. Reports were acquired from the Coroner’s Court, Police Force, and Education Bureau in Hong Kong. Information about students’ sociodemographic characteristics, suicide circumstances, stressors, and risk factors was extracted and organized for analysis. Based on the indicated stressors (school, family, close relationship, social challenge, finance, risk behaviour, suicide exposure, others) and risk factors (health and mental health, history of self-harm, suicidality, and psychological maladjustment), cluster analysis was conducted to derive distinct profiles of student suicides.

Results

A four-cluster solution was found. Patterns of stressors, risk factors, background characteristics and suicide circumstances within each cluster were examined. Four distinct and meaningful profiles of student suicides were characterised as “school distress”, “hidden”, “family and relationship”, and “numerous issues”.

Conclusions

Findings highlighted the need to approach student suicides in meaningfully differentiated ways. Gathering suicide report data and generating evidence that advances our knowledge of student suicide profiles are important steps towards early identification and intervention.
Broadening the scope of social support, coping skills and resilience among caretakers of children with disabilities in Uganda: a sequential explanatory mixed-methods study
Authors: Namasaba Mariam , Kazembe Neo , Seera Georgina , Baguwemu Ali Ayub
Published: April 2022

Background

Most caretakers of children with disabilities (CWDs) have adverse health outcomes. Approximately 31% of the caretakers have clinical depression in the world. In Sub-Saharan Africa, 42% of them face severe psychological distress. Caretakers in Africa face additional cultural challenges that undermine their coping skills, access to social support, and resilience.

Methods

This study used sequential explanatory mixed methods to examine the relationships of social support, coping skills and resilience among caretakers of CWDs in Uganda. A total of 621 caretakers were surveyed, and 43 of them participated in interviews. Hierarchical cluster analysis and binary logistic regression were conducted to determine coping patterns and predict caretakers’ likelihood of using them. Hierarchical linear regression and thematic analyses then explored the relationships and perceptions of coping skills and resilience related to social support. A joint display was used to integrate results and show the convergence and expansion of quantitative and qualitative results.

Results

Quantitative and qualitative findings converged that caretakers who received social support used adaptive coping skills and had higher resilience. Qualitative results expanded the finding that caretakers who received formal social support perceived it as a safer mode of care than informal social support.

Conclusions

The study expanded the scope of social support, coping skills, and resilience. Caretakers perceived formal social support from schools as a safe mode of care that enabled them to use adaptive coping skills and have high resilience. Therefore, enrolling children with disabilities in schools at an early age is beneficial for building the resilience of their caretakers.
Adolescence exposure to China’s great famine period and the association of metabolic syndrome in adulthood: a retrospective study
Authors: Sun Ning , Li Wei , Osibogun Olatokunbo , Kalan Mohammad Ebrahimi , Jebai Rime , Gautam Prem , Taskin Tanjila , Yin Wupeng , Jones Jeffery A. , Gamber Michelle , Sun Wenjie
Published: April 2022

Background

Exposure to famine during early life is related to several adverse health outcomes in adulthood, but the effect of famine exposure during adolescence is unclear. This study aims to examine whether exposure to famine in adolescence is associated with metabolic syndrome (MetS) in adulthood.

Methods

This study included 4130 Chinese adults (2059 males and 2071 females) aged 59–71 from the 2011 China Health and Retirement Longitudinal Study (CHARLS). All the selected participants were exposed to the three-year time period (1959–1961) of China’s Great Famine. Participants were categorized into an adolescent-exposed group (born 01/01/1944–12/31/1948) and a non-adolescent-exposed group (born 01/01/1940–12/31/1941 and 01/01/1951–12/31/1952). Sex-stratified multiple logistic regression models were used to estimate the association between exposure to famine in adolescence and MetS.

Results

Participants exposed to famine during adolescence were more likely to report MetS (aOR = 1.35; 95%CI 1.01–1.78) compared to the non-adolescent-exposed group. Further, males were 45% less likely to report MetS than females (aOR = 0.55; 95%CI 0.36–0.83). After stratification by sex, the effects of famine exposure during adolescence on MetS were detected among males only (aOR = 1.97; 95%CI 1.20–3.24). Additionally, males with a history of drinking were more likely to report MetS compared to those with no history of drinking (aOR = 2.63; 95%CI 1.41–4.90).

Conclusions

Our findings reveal that exposure to famine during adolescence is associated with higher odds of MetS in adulthood overall, and this association is only pronounced among males. This study emphasizes that undernutrition in early life, including adolescence, may have a long-term effect and be associated with adverse health events in middle-to-late life. Targeting those elderly people who suffered famine during adolescence may help prevent the development of MetS in later life.
Risk factors of knee osteoarthritis in Bangladeshi adults: a national survey
Authors: Haider Mohammad Ziaul , Bhuiyan Rijwan , Ahmed Shamim , Zahid-Al-Quadir Ahmad , Choudhury Minhaj Rahim , Haq Syed Atiqul , Zaman Mohammad Mostafa
Published: April 2022

Background

Knee osteoarthritis was reported as the second most prevalent condition in the national musculoskeletal survey. The purpose of this extended study was to identify risk factors for knee osteoarthritis in Bangladeshi adults.

Methods

This cross-sectional study was conducted in rural and urban areas of Bangladesh using stratified multistage cluster sample of 2000 adults aged 18 years or older recruited at their households. The Modified Community Oriented Program for Control of Rheumatic Disorders (COPCORD) questionnaire was used to collect data. The diagnosis of knee osteoarthritis was made using the decision tree clinical categorization criteria of the American College of Rheumatology. Univariate and multivariate logistic regression analyses were done to identify the risk factors for knee osteoarthritis.

Results

A total of 1843 individuals (892 men and 951 women) participated, and 134 had knee osteoarthritis yielding a prevalence of 7.3% (95% confidence interval (CI) 4.9 to 9.6%). The mean (standard deviation) age of the knee osteoarthritis patients was 51.7 (11.2) years. Multivariate logistic regression analysis found a significant association with increasing age (≥38 years OR 8.9, 95% CI 4.8–16.5; ≥58 years OR 13.9, 95% CI 6.9–28.0), low educational level (OR 1.7, 95% CI 1.0–2.7) and overweight (OR 1.9, 95% CI 1.2–2.9) with knee osteoarthritis. Knee osteoarthritis patients had a high likelihood of having work loss preceding 12 months (age and sex-adjusted OR 2.3; 95% CI 1.4–3.8; P < 0.01).

Conclusions

Knee osteoarthritis is a commonly prevalent musculoskeletal problem among Bangladeshi adults having link to work loss. Increasing age, low education and overweight are significant risk factors of knee osteoarthritis.
Skeletal and alveolar changes in conventional rapid palatal expansion (RPE) and miniscrew-assisted RPE (MARPE): a prospective randomized clinical trial using low-dose CBCT
Authors: Chun Joo-Hee , de Castro Amanda Cunha Regal , Oh Sunmee , Kim Kyung-Ho , Choi Sung-Hwan , Nojima Lincoln Issamu , Nojima Matilde da Cunha Gonçalves , Lee Kee-Joon
Published: April 2022

Background

This prospective randomized clinical trial aimed to evaluate the immediate and short-term skeletal, dentoalveolar, and periodontal effects of rapid palatal expansion (RPE) and miniscrew-assisted RPE (MARPE) in adolescent and young adult patients.

Methods

This study followed a two-arm, parallel, randomized clinical trial design that recruited patients with transverse maxillary deficiency in a 1:1 allocation ratio. Forty patients (14 men and 26 women) requiring maxillary expansion were randomly allocated to the RPE (n = 20, age = 14.0 ± 4.5) or MARPE (n = 20, age = 14.1 ± 4.2) groups. The assignment was performed via computer-generated block randomization, with a block size of four. Upon identical (35 turns) amount of expansion, low-dose cone-beam computed tomography images were taken before treatment (T0), immediately after expansion (T1), and after a 3-month consolidation period (T2). The primary outcome of this study comprised the assessment of midpalatal suture separation. Secondary outcomes included, skeletal, dentoalveolar, and periodontal measurements, which were performed at each time point.

Results

The frequency of midpalatal suture separation was 90% (18/20) and 95% (19/20) for the RPE and MARPE groups, respectively. A greater increase in nasal width in the molar region (M-NW) and greater palatine foramen (GPF) was observed immediately after the expansion (T1-T0) and consolidation periods (T2-T0) in the MARPE group compared to the RPE group (P < 0.05). The MARPE and RPE groups showed similar dentoalveolar changes except for the maxillary width (PM-MW, M-MW). The MARPE group presented greater bilateral first premolar (PM-MW) and molar (M-MW) maxillary width in relation to the RPE group (P < 0.05). Through the expansion and consolidation periods (T2-T0), lesser buccal displacement of the anchor teeth was observed in the MARPE group (PM-BBPT, PM-PBPT, M-BBPT [mesial and distal roots], and M-PBPT)( P < 0.05).

Conclusions

Midpalatal suture separation was observed in 90% and 95% of patients in the RPE and MARPE groups, respectively. Both RPE and MARPE groups exhibited significant triangular basal bone expansion and skeletal relapse during consolidation. Under identical amounts of expansion, the MARPE group showed lower decrease in the skeletal, dentoalveolar and periodontal variables after consolidation. The reinforcement of RPE with miniscrews contributes to the maintenance of the basal bone during consolidation period.

Trial registration WHO Institutional Clinical Trials Registry Platform (IRB No. KCT0006871 / Registration date 27/12/2021).
Improving care for cancer-related and other forms of lymphoedema in low- and middle-income countries: a qualitative study
Authors: Torgbenu Eric , Luckett Tim , Buhagiar Mark , Requena Cecilia Mauricio , Phillips Jane L.
Published: April 2022

Background

Lymphoedema is a common, distressing and debilitating condition that can be related to cancer and its treatment or other conditions. Little is known about current practices in the diagnosis, assessment and management of lymphoedema in low- and middle-income countries (LMIC).

Aim

To describe current practices in diagnosing, assessing and managing cancer-related and other forms of lymphoedema in LMIC, and related barriers and facilitators.

Methods

An exploratory-descriptive qualitative study. Participants were lymphoedema experts or health care professionals identified via published lymphoedema papers and professional organizations respectively. Sampling was purposive to ensure a diversity of perspectives and experience. Data collection was via semi-structured telephone/video interviews, and questions canvassed participants’ experiences and perceptions of lymphoedema care in LMIC. Interviews were audio-recorded and transcribed verbatim. Analysis proceeded via inductive coding before mapping codes to the World Health Organization’s (WHO) Innovative Care for Chronic Conditions Framework.

Results

Nineteen participants were interviewed, most of whom were physiotherapists (n = 11). Ten participants worked permanently in a LMIC, while the remainder were based in a high-income country (HIC) and had been involved in initiatives to improve lymphoedema care across multiple LMIC. Participants indicated that management of cancer versus non-cancer related lymphoedema was similar, but that pathways to care were more straight-forward for those receiving cancer care, leading to earlier diagnosis. Key facilitators to optimizing lymphoedema care in LMIC included: 1) joining forces to overcome lymphoedema-related stigma; 2) building workforce capabilities; and 3) partnering with patients and families to support self-management. Ideas for building workforce included developing health professional knowledge, supporting a commitment to multidisciplinary team care, and adapting HIC guidelines for lymphoedema care to LMIC. Partnering with patients and families to support self-management involved following the person-centred approach, establishing clear communication, promoting adherence to management, adapting management to available resources, and involving patient family and friends in lymphoedema care.

Conclusion

Raising community and health professional awareness regarding lymphoedema and its management is a key first step to improving care outcomes. Resources for clinicians and patients/families developed for lymphoedema care in HIC need to be adapted for low resource settings.
Non-compliance with a nurse’s advice to visit the primary care provider: an exploratory secondary analysis of the TRIAGE-trial
Authors: Homburg Ines , Morreel Stefan , Verhoeven Veronique , Monsieurs Koenraad G. , Meysman Jasmine , Philips Hilde , De Graeve Diana
Published: April 2022

Background

During the cluster randomised TRIAGE-trial, a nurse advised 13% of low-risk patients presenting at an emergency department in Belgium to visit the adjacent general practitioner cooperative. Patients had the right to refuse this advice. This exploratory study examines the characteristics of refusers by uncovering the determinants of non-compliance and its impact on costs, as charged on the patient’s invoice.

Methods

Bivariate analyses with logistic regressions and T-tests were used to test the differences in patient characteristics, patient status, timing characteristics, and costs between refusers and non-refusers. A chi-square automatic interaction detection analysis was used to find the predictors of non-compliance.

Results

23.50% of the patients refused the advice to visit the general practitioner cooperative. This proportion was mainly influenced by the nurse on duty (non-compliance rates per nurse ranging from 2.9% to 52.8%) and the patients’ socio-economic status (receiving increased reimbursement versus not OR 1.37, 95%CI: 0.96 to 1.95). Additionally, non-compliance was associated (at the 0.10 significance level) with being male, not living nearby and certain reasons for encounter. Fewer patients refused when the nurse perceived crowding level as quiet relative to normal, and more patients refused during the evening. The mean cost was significantly higher for patients who refused, which was a result of more extensive examination and higher out-of-pocket expenses at the ED.

Conclusions

The nurse providing the advice to visit the general practitioner cooperative has a central role in the likelihood of patients’ refusal. Interventions to reduce non-compliance should aim at improving nurse-patient communication. Special attention may be required when managing patients with a lower socio-economic status. The overall mean cost was higher for refusers, illustrating the importance of compliance.

Trial registration

The trial was registered on registration number NCT03793972 on 04/01/2019.
Plant metabolomics: a new strategy and tool for quality evaluation of Chinese medicinal materials
Authors: Xiao Qi , Mu Xinlu , Liu Jiushi , Li Bin , Liu Haitao , Zhang Bengang , Xiao Peigen
Published: April 2022

The present quality control method of Chinese medicinal materials (CMM) has obvious deficiency, which cannot be compatible with the multi-target and multi-component characteristics and production process of CMM. Plant metabolomics with a huge impetus to comprehensively characterize the metabolites and clarify the complexity and integrity of CMM, has been widely used in the research of CMM. This article comprehensively reviewed the application of plant metabolomics in the quality control of CMM. It introduced the concept, technique, and application examples, discussed the prospects, limitations, improvements of plant metabolomics. MS and NMR, as important techniques for plant metabolomics, are mainly highlighted in the case references. The purpose of this article is to clarify the advantage of plants metabolomics for promoting the optimization of the CMM quality control system and proposing a system approach to realize the overall quality control of CMM based on plant metabolomics combined with multidisciplinary method.
Multimarker synaptic protein cerebrospinal fluid panels reflect TDP-43 pathology and cognitive performance in a pathological cohort of frontotemporal lobar degeneration
Authors: Cervantes González Alba , Irwin David J. , Alcolea Daniel , McMillan Corey T. , Chen-Plotkin Alice , Wolk David , Sirisi Sònia , Dols-Icardo Oriol , Querol-Vilaseca Marta , Illán-Gala Ignacio , Santos-Santos Miguel Angel , Fortea Juan , Lee Edward B. , Trojanowski John Q. , Grossman Murray , Lleó Alberto , Belbin Olivia
Published: April 2022

Background

Synapse degeneration is an early event in pathological frontotemporal lobar degeneration (FTLD). Consequently, a surrogate marker of synapse loss could be used to monitor early pathologic changes in patients with underlying FTLD. The aim of this study was to evaluate the relationship of antemortem cerebrospinal fluid (CSF) levels of 8 synaptic proteins with postmortem global tau and TDP-43 burden and cognitive performance and to assess their diagnostic capacity in a neuropathological FTLD cohort.

Methods

We included patients with a neuropathological confirmation of FTLD-Tau (n = 24, mean age-at-CSF 67 years ± 11), FTLD-TDP (n = 25, 66 years ± 9) or AD (n = 25, 73 years ± 6) as well as cognitively normal controls (n = 35, 69 years ± 7) from the Penn FTD Center and ADRC. We used a semi-quantitative measure of tau and TDP-43 inclusions to quantify pathological burden across 16 brain regions. Statistical methods included Spearman rank correlations, one-way analysis of covariance, ordinal regression, step-wise multiple linear regression and receiver-operating characteristic curves.

Result

CSF calsyntenin-1 and neurexin-2a were correlated in all patient groups (rs = .55 to .88). In FTLD-TDP, we observed low antemortem CSF levels of calsyntenin-1 and neurexin-2a compared to AD (.72-fold, p = .001, .77-fold, p = .04, respectively) and controls (.80-fold, p = .02, .78-fold, p = .02, respectively), which were inversely associated with post-mortem global TDP-43 burden (regression r2 = .56, p = .007 and r2 = .57, p = .006, respectively). A multimarker panel including calsyntenin-1 was associated with TDP-43 burden (r2 = .69, p = .003) and MMSE score (r2 = .19, p = .03) in FTLD. A second multimarker synaptic panel, also including calsyntenin-1, was associated with MMSE score in FTLD-tau (r2 = .49, p = .04) and improved diagnostic performance to discriminate FTLD-Tau and FTLD-TDP neuropathologic subtypes (AUC = .83).

Conclusion

These synaptic panels have potential in the differential diagnosis of FTLD neuropathologic subtypes and as surrogate markers of cognitive performance in future clinical trials targeting TDP-43 or tau.
Adaptive antitumor immune response stimulated by bio-nanoparticle based vaccine and checkpoint blockade
Authors: Bai Xuewei , Zhou Yanmei , Yokota Yuki , Matsumoto Yoshihiro , Zhai Bo , Maarouf Nader , Hayashi Hikaru , Carlson Rolf , Zhang Songhua , Sousa Aryanna , Sun Bei , Ghanbari Hossein , Dong Xiaoqun , Wands Jack R.
Published: April 2022

Background

Interactions between tumor and microenvironment determine individual response to immunotherapy. Triple negative breast cancer (TNBC) and hepatocellular carcinoma (HCC) have exhibited suboptimal responses to immune checkpoint inhibitors (ICIs). Aspartate β-hydroxylase (ASPH), an oncofetal protein and tumor associated antigen (TAA), is a potential target for immunotherapy.

Methods

Subcutaneous HCC and orthotopic TNBC murine models were established in immunocompetent BALB/c mice with injection of BNL-T3 and 4 T1 cells, respectively. Immunohistochemistry, immunofluorescence, H&E, flow cytometry, ELISA and in vitro cytotoxicity assays were performed.

Results

The ASPH-MYC signaling cascade upregulates PD-L1 expression on breast and liver tumor cells. A bio-nanoparticle based λ phage vaccine targeting ASPH was administrated to mice harboring syngeneic HCC or TNBC tumors, either alone or in combination with PD-1 blockade. In control, autocrine chemokine ligand 13 (CXCL13)-C-X-C chemokine receptor type 5 (CXCR5) axis promoted tumor development and progression in HCC and TNBC. Interactions between PD-L1+ cancer cells and PD-1+ T cells resulted in T cell exhaustion and apoptosis, causing immune evasion of cancer cells. In contrast, combination therapy (Vaccine+PD-1 inhibitor) significantly suppressed primary hepatic or mammary tumor growth (with distant pulmonary metastases in TNBC). Adaptive immune responses were attributed to expansion of activated CD4+ T helper type 1 (Th1)/CD8+ cytotoxic T cells (CTLs) that displayed enhanced effector functions, and maturation of plasma cells that secreted high titers of ASPH-specific antibody. Combination therapy significantly reduced tumor infiltration of immunosuppressive CD4+/CD25+/FOXP3+ Tregs. When the PD-1/PD-L1 signal was inhibited, CXCL13 produced by ASPH+ cancer cells recruited CXCR5+/CD8+ T lymphocytes to tertiary lymphoid structures (TLSs), comprising effector and memory CTLs, T follicular helper cells, B cell germinal center, and follicular dendritic cells. TLSs facilitate activation and maturation of DCs and actively recruit immune subsets to tumor microenvironment. These CTLs secreted CXCL13 to recruit more CXCR5+ immune cells and to lyse CXCR5+ cancer cells. Upon combination treatment, formation of TLSs predicts sensitivity to ICI blockade. Combination therapy substantially prolonged overall survival of mice with HCC or TNBC.

Conclusions

Synergistic antitumor efficacy attributable to a λ phage vaccine specifically targeting ASPH, an ideal TAA, combined with ICIs, inhibits tumor growth and progression of TNBC and HCC.
Effectiveness of an app-based intervention to reduce substance use, gambling, and digital media use in vocational school students: study protocol for a randomized controlled trial
Authors: Arnaud Nicolas , Weymann Johanna , Lochbühler Kirsten , Pietsch Benjamin , Rossa Monika , Kraus Ludwig , Thomasius Rainer , Hanewinkel Reiner , Morgenstern Matthis
Published: April 2022

Background

Substance-related and addictive disorders are among the most common mental disorders in adolescence and young adulthood. Vocational school students are a risk group for problematic substance use and addictive behavior. However, the availability of evidence-based prevention concepts and programs is underdeveloped in the vocational school setting.

Methods/design

A two-arm cluster randomized waitlist-controlled trial will be conducted to evaluate the effectiveness of an app-based intervention to decrease substance use, gambling, and digital media use in vocational school students in Germany. Vocational students will participate in an app-based intervention that is designed to support voluntary commitment to abstain from or reduce substance or digital media use over a period of 2 weeks. The “education-as-usual” control arm will have access to the intervention after data collection is completed. One of the primary outcome measures will be the use of alcohol, nicotine, and digital media 30 days after the intervention. Several secondary outcome measures will also be included, such as cannabis consumption, gambling, symptoms of stress, physical activity, mindfulness, well-being, impulsivity and sensation seeking, and readiness to change. A total of 4500 vocational students from 225 classes will be recruited and randomized across three German federal states.

Discussion

This study protocol describes the design of an RCT testing the effectiveness of an app-based intervention to reduce addictive behaviors in vocational school students. It is expected that this approach will be feasible for and effective in the vocational school setting and that the study provides comprehensive information on the key factors involved in temporary abstaining or reducing substance or digital media use.

Trial registration

German Clinical Trials Register DRKS00023788. Registered on 20 January 2021
The effect of glycerol as a cryoprotective agent in the cryopreservation of adipose tissue
Authors: Zhang Pei-Qi , Tan Poh-Ching , Gao Yi-Ming , Zhang Xiao-Jie , Xie Yun , Zheng Dan-Ning , Zhou Shuang-Bai , Li Qing-Feng
Published: April 2022

Background

Long-term preservation of adipose tissue is crucial for clinical applications. Researchers should consider both efficiency and biosafety when choosing a cryoprotective agent (CPA) for adipose tissue preservation. Glycerol has been applied as a nontoxic CPA for multiple tissues but not adipose tissue. We aimed to evaluate the efficacy of glycerol as a CPA for adipose tissue cryopreservation.

Methods

Fresh human adipose tissues were obtained from patients who underwent liposuction and divided into 1 mL samples. Each sample was randomly mixed with 1 mL of CPA: 60–100% glycerol, 0.25 mol/L trehalose or DMSO + FBS and cryopreserved in − 196 °C liquid nitrogen for one month. After thawing and elution, the tissues were immediately evaluated for activity and structural integrity in vitro. Then, 0.2 mL of each sample was transplanted subdermally to the nude mouse dorsum and harvested after one month for histological examination to assess the effect of the cryopreserved fat in transplantation.

Results

After cryopreservation, the samples treated with DMSO + FBS, trehalose, 60% and 70% glycerol had a more integrated structure than the samples in other groups. Tissues preserved with 70% glycerol had the highest G3PDH activity of 24.41 ± 0.70, comparable to 24.76 ± 0.48 in fresh tissue (p > 0.05). Adipose-derived stem cells (ASC) viability, proliferation and differentiation capability were also better preserved in 70% glycerol group. In vivo analysis showed that tissue preserved with 70% glycerol had a retention rate of 52.37 ± 7.53%, significantly higher than other groups. Histological observation demonstrated better structural integrity and viability in 70% glycerol group. Compared to the DMSO + FBS and trehalose groups, the glycerol groups showed lower tissue inflammation.

Conclusion

Glycerol (70%) is efficient in adipose tissue cryopreservation. Glycerol-based CPAs, which are nontoxic and show biosafety, are a promising solution for clinical tissue cryopreservation.
Human primitive mesenchymal stem cell-derived retinal progenitor cells improved neuroprotection, neurogenesis, and vision in rd12 mouse model of retinitis pigmentosa
Authors: Brown Christina , Agosta Patrina , McKee Christina , Walker Keegan , Mazzella Matteo , Alamri Ali , Svinarich David , Chaudhry G. Rasul
Published: April 2022

Background

Currently, there is no treatment for retinal degenerative diseases (RDD) such as retinitis pigmentosa (RP). Stem cell-based therapies could provide promising opportunities to repair the damaged retina and restore vision. Thus far, primarily adult mesenchymal stem cells (MSCs) have been investigated in preclinical and clinical studies, and the results have not been convincing. We applied a new approach in which primitive (p) MSC-derived retinal progenitor cells (RPCs) were examined to treat retinal degeneration in an rd12 mouse model of RP.

Methods

Well-characterized pMSCs and RPCs labeled with PKH26 were intravitreally injected into rd12 mice. The vision and retinal function of transplanted animals were analyzed using electroretinography. Animals were killed 4 and 8 weeks after cell transplantation for histological, immunological, molecular, and transcriptomic analyses of the retina.

Results

Transplanted RPCs significantly improved vision and retinal thickness as well as function in rd12 mice. pMSCs and RPCs homed to distinct retinal layers. pMSCs homed to the retinal pigment epithelium, and RPCs migrated to the neural layers of the retina, where they improved the thickness of the respective layers and expressed cell-specific markers. RPCs induced anti-inflammatory and neuroprotective responses as well as upregulated the expression of genes involved in neurogenesis. The transcriptomic analysis showed that RPCs promoted neurogenesis and functional recovery of the retina through inhibition of BMP and activation of JAK/STAT and MAPK signaling pathways.

Conclusions

Our study demonstrated that RPCs countered inflammation, provided retinal protection, and promoted neurogenesis resulting in improved retinal structure and physiological function in rd12 mice.
Short-term responses of herbaceous vegetation to bush clearing in semi-arid rangelands of South Africa
Authors: Mndela Mthunzi , Madakadze Ignacio C. , Nherera-Chokuda Florence V. , Dube Sikhalazo , Ramoelo Abel , Mangwane Mziwanda , Tjelele Julius T.
Published: April 2022

Bush thickening reduces herbaceous species diversity and forage production, leading to a decline in grazing capacity. Hence, altering the micro-climate and woody-grass competition in bush-encroached rangelands using bush clearing is instrumental for the restoration of herbaceous vegetation. The short-term recovery potential of herbaceous species composition, basal cover and biomass production was assessed following bush clearing at Makapaanstad, North West province, South Africa. The mean density was 6908 woody plants ha−1, with Vachellia tenuispina encroaching at 6301 plants ha−1. Paired observations were conducted in bush-cleared sites (where woody plants were cut using saws, with stumps treated with picloram at 1% concentration) and uncleared sites (where the woody cover was left intact). Forty-nine different herbaceous species were recorded, with grasses being more abundant in cleared (62%) than in uncleared sites (50%). Herbaceous species showed interspecific responses, with Brachiaria eruciformis and Panicum coloratum colonising in cleared sites, whereas the frequency of other species remained comparable between cleared and uncleared sites. Graminoids, largely bunch grasses, had a significantly greater basal cover in cleared (496 cm2 m−2) compared to uncleared (301 cm2 m−2) sites. Likewise, total biomass production was significantly (p = 0.05) higher in cleared (760 kg DM ha−1) than in uncleared (636 kg DM ha−1) sites. The principal component analysis (PCA) showed that most herbaceous species were associated with soils having high total nitrogen and nitrite. Seedlings of forbs (r2 = 0.81), grasses (r2 = 0.97) and succulents (r2 = 0.98) were highly associated with nitrate-rich soils. Our results revealed that even at a short term, bush clearing is important for the restoration of herbaceous vegetation.
Evaluation of the importance of mixing during preparation of antibiotic infusions
Authors: Barzel Ina , Jessurun Janique Gabriëlle , Bahmany Soma , van der Kuy Paul Hugo Marie , Koch Birgit Catharina Peter , Hunfeld Nicole Geertruida Maria
Published: April 2022

Background

The mixing step after medication addition to the infusion bag is frequently omitted during the preparation of drug infusions. However, the importance of mixing when preparing antibiotic infusions is still unknown.

Methods

The primary aim of this study was to assess the importance of the mixing step by comparing the concentrations of unmixed antibiotic infusions (cefuroxime, flucloxacillin, meropenem, and vancomycin) with the declared concentration at regular intervals during infusion. The secondary aim was to compare concentrations between preparation sites (hospital pharmacy versus clinical ward). Infusion bags were run through electronic infusion pumps. For cefuroxime, flucloxacillin, and meropenem, samples were collected 1, 15, and 20 min after starting the administration (infusion duration: 30 min). For vancomycin, samples were collected after 1, 60, and 110 min (infusion duration: 120 min). Vancomycin concentrations were measured using the Architect c4000 analyser and other concentrations using a validated UPC2-MS–MS multimethod.

Results

The median concentrations of the four antibiotics were comparable to the declared concentration at all three time points. No significant differences were found between preparation sites.

Conclusions

Spontaneous mixing occurred in the examined antibiotic solutions during normal handling.