bluuebunny/crossref_metadata_2025 huggingface dataset:
Effectiveness and safety of dermal matrix used for diabetic foot ulcer: a systematic review and meta-analysis of randomized controlled trials
Authors: Sui Lei , Xie Qiang , Jiang Hong-tao , Li Xiao-dong
Published: February 2024

Background

Diabetic foot ulcers (DFUs) have become a global health concern, which can lead to diabetic foot infection (DFI), lower leg amputation, and even mortality. Though the standard of care (SOC) practices have been recognized as the “gold standard” for DFU care, SOC alone may not be adequate to heal all DFUs and prevent their recurrence. The use of dermal matrix has emerged as an adjuvant treatment to enhance DFU healing. The current study aimed to evaluate the effectiveness and safety of dermal matrix application as an adjuvant treatment to the SOC.

Methods

The databases of PubMed, Embase and CENTRAL were independently searched by two authors, with the following key terms: “diabetic foot ulcer”, “acellular dermal matrix”, “wound healing”, and so on. Randomized controlled trials (RCTs) evaluated the efficacy and safety of dermal matrix in the treatment of DFUs were eligible for inclusion. The primary outcomes analyzed included time to complete healing and complete healing rate at the final follow-up, while secondary outcomes included wound area, ulcer recurrence rate, amputation risk and complication risk. Meta-analyses were performed using random-effect or fixed-effect models, based on the heterogeneity test.

Results

This study included a total of 15 RCTs with a total of 1524 subjects. Of these, 689 patients were treated with SOC alone, while 835 patients received SOC plus dermal matrix. Compared to the SOC group, significantly shorter time (MD = 2.84, 95%CI: 1.37 ~ 4.32, p < 0.001***) was required to achieve complete healing in dermal matrix group. Significantly higher complete healing rate (OR = 0.40, 95%CI: 0.33 ~ 0.49, p < 0.001***) and lower overall (RR = 1.83, 95%CI: 1.15 ~ 2.93, p = 0.011*) and major (RR = 2.64, 95%CI: 1.30 ~ 5.36, p = 0.007**) amputation risks were achieved in dermal matrix group compared to SOC group. No significant difference was found in the wound area, ulcer recurrence rate, and complication risk between the two groups.

Conclusions

The application of dermal matrix as an adjuvant therapy in conjunction with SOC effectively improved the healing process of DFUs and reduced the amputation risk when compared to SOC alone. Furthermore, dermal matrix application was well tolerated by the subjects with no added complication risk.
Unraveling the challenges in the diagnosis and management of desmoplastic fibroma of the mandible–a case report
Authors: Siddiqui Humayun Kaleem , Khan Shahrukh Ali , Aijaz Anum , Qureshi Madiha Bilal
Published: February 2024

Desmoplastic fibroma (DF) is an uncommon bone tumor that originates from the mesenchymal tissue and despite being benign, exhibits aggressive behavior locally. The following report describes the case of a 7-year-old boy with a rapidly enlarging swelling on the right side of the mandible. After a thorough clinical examination, radiographic imaging, and histopathological analysis, the diagnosis of DF was confirmed. Treatment planning was formulated considering both the tumor’s tendency for local recurrence and the patient’s well-being. Due to the patient’s young age, segmental resection was not deemed appropriate, and an aggressive curettage and enucleation of the lesion followed by the bone graft was performed instead. The patient was kept under close follow-up for the first month of post-surgery and later reviewed after 3, 6, 9, and 12 months, respectively. Good bone healing was observed on radiographs. The patient did not show any signs of recurrence based on clinical or radiographic assessments and did not exhibit any neurosensory deficits as well.
An intelligent grasper to provide real-time force feedback to shorten the learning curve in laparoscopic training
Authors: Huang Xuemei , Wang Pingping , Chen Jie , Huang Yuxin , Liao Qiongxiu , Huang Yuting , Liu Zhengyong , Peng Dongxian
Published: February 2024

Background

A lack of force feedback in laparoscopic surgery often leads to a steep learning curve to the novices and traditional training system equipped with force feedback need a high educational cost. This study aimed to use a laparoscopic grasper providing force feedback in laparoscopic training which can assist in controlling of gripping forces and improve the learning processing of the novices.

Methods

Firstly, we conducted a pre-experiment to verify the role of force feedback in gripping operations and establish the safe gripping force threshold for the tasks. Following this, we proceeded with a four-week training program. Unlike the novices without feedback (Group A2), the novices receiving feedback (Group B2) underwent training that included force feedback. Finally, we completed a follow-up period without providing force feedback to assess the training effect under different conditions. Real-time force parameters were recorded and compared.

Results

In the pre-experiment, we set the gripping force threshold for the tasks based on the experienced surgeons’ performance. This is reasonable as the experienced surgeons have obtained adequate skill of handling grasper. The thresholds for task 1, 2, and 3 were set as 0.731 N, 1.203 N and 0.938 N, respectively. With force feedback, the gripping force applied by the novices with feedback (Group B1) was lower than that of the novices without feedback (Group A1) (p < 0.005). During the training period, the Group B2 takes 6 trails to achieve gripping force of 0.635 N, which is lower than the threshold line, whereas the Group A2 needs 11 trails, meaning that the learning curve of Group B2 was significantly shorter than that of Group A2. Additionally, during the follow-up period, there was no significant decline in force learning, and Group B2 demonstrated better control of gripping operations. The training with force feedback received positive evaluations.

Conclusion

Our study shows that using a grasper providing force feedback in laparoscopic training can help to control the gripping force and shorten the learning curve. It is anticipated that the laparoscopic grasper equipped with FBG sensor is promising to provide force feedback during laparoscopic training, which ultimately shows great potential in laparoscopic surgery.
Layered vulnerability and researchers’ responsibilities: learning from research involving Kenyan adolescents living with perinatal HIV infection
Authors: Kimani Mary , Molyneux Sassy , Charo Anderson , Zakayo Scholastica M. , Sanga Gladys , Njeru Rita , Davies Alun , Kelley Maureen , Abubakar Amina , Marsh Vicki
Published: February 2024

Background

Carefully planned research is critical to developing policies and interventions that counter physical, psychological and social challenges faced by young people living with HIV/AIDS, without increasing burdens. Such studies, however, must navigate a ‘vulnerability paradox’, since including potentially vulnerable groups also risks unintentionally worsening their situation. Through embedded social science research, linked to a cohort study involving Adolescents Living with HIV/AIDS (ALH) in Kenya, we develop an account of researchers’ responsibilities towards young people, incorporating concepts of vulnerability, resilience, and agency as ‘interacting layers’.

Methods

Using a qualitative, iterative approach across three linked data collection phases including interviews, group discussions, observations and a participatory workshop, we explored stakeholders’ perspectives on vulnerability and resilience of young people living with HIV/AIDS, in relation to home and community, school, health care and health research participation. A total of 62 policy, provider, research, and community-based stakeholders were involved, including 27 ALH participating in a longitudinal cohort study. Data analysis drew on a Framework Analysis approach; ethical analysis adapts Luna’s layered account of vulnerability.

Results

ALH experienced forms of vulnerability and resilience in their daily lives in which socioeconomic context, institutional policies, organisational systems and interpersonal relations were key, interrelated influences. Anticipated and experienced forms of stigma and discrimination in schools, health clinics and communities were linked to actions undermining ART adherence, worsening physical and mental health, and poor educational outcomes, indicating cascading forms of vulnerability, resulting in worsened vulnerabilities. Positive inputs within and across sectors could build resilience, improve outcomes, and support positive research experiences.

Conclusions

The most serious forms of vulnerability faced by ALH in the cohort study were related to structural, inter-sectoral influences, unrelated to study participation and underscored by constraints to their agency. Vulnerabilities, including cascading forms, were potentially responsive to policy-based and interpersonal actions. Stakeholder engagement supported cohort design and implementation, building privacy, stakeholder understanding, interpersonal relations and ancillary care policies. Structural forms of vulnerability underscore researchers’ responsibilities to work within multi-sectoral partnerships to plan and implement studies involving ALH, share findings in a timely way and contribute to policies addressing known causes of vulnerabilities.
Educating the nurses of tomorrow: exploring first-year nursing students’ reflections on a one-week senior peer-mentor supervised inspiration practice in nursing homes
Authors: Lillekroken Daniela , Kvalvaag Heidi M. , Lindeflaten Katrin , Flølo Tone Nygaard , Krogstad Kristine , Hessevaagbakke Elisabeth
Published: February 2024

Background

Worldwide, the healthcare system stresses a severe deficit of nurses because of elevated levels of work-induced stress, burnout and turnover rates, as well as the ageing of the nursing workforce. The diminishing number of nursing students opting for a career in nursing older people has exacerbated this shortage. A determining factor in the choice of a career within the field of residential care for nursing students is educational institutions offering students learning opportunities with positive learning experiences. Therefore, educational institutions must develop programmes that employ student active learning methods during clinical periods. Although much focus has been given to the development of new educational programs, insufficient consideration has been given to the value of peer mentoring and students’ interactions during the clinical placement at nursing homes. The aim of the present study is to explore first-year nursing students’ perceptions and experiences with peer mentoring as an educational model during their inspiration practice week at nursing home.

Methods

The study employed a qualitative exploratory and descriptive research design. Data collection took place in October 2022 using focus group interviews. A total of 53 students in their first year of the bachelor’s programme at the Oslo Metropolitan University participated in eight focus group interviews. The data were analysed following the principles of inductive content analysis.

Results

The analysis resulted in one main category, ‘Being inspired—keep learning and moving forward’, representing first-year nursing students’ common perceptions of being mentored by third-year students. The main category is supported by two categories: ‘Closeness to the mentor’ and ‘Confidence in mentors’ professional knowledge and teaching and supervision methods’, which are interpreted as the drivers that enabled first-year students to learn more about nurses’ roles and responsibilities in the nursing home.

Conclusion

Mentorship enhances the learning transfer from third-year nursing students over to first-year nursing students by providing them with real-world exposure and guidance from their more experienced peers. This hands-on approach allows them to bridge the gap between theory and practice more effectively, boosting first-year nursing students’ confidence and competence in nursing and caring for older people living in nursing homes.
Characteristics and risk factors of pharmacist misconduct in New Zealand: a retrospective nationwide analysis
Authors: Wang Yufeng , Ram Sanyogita , Scahill Shane
Published: February 2024

Background

Professional misconduct has evolved into a worldwide concern, involving various forms and types of behaviours that contribute to unsafe practices. This study aimed to provide insights into the patterns characterising pharmacist misconduct and uncover underlying factors contributing to such instances in New Zealand.

Methods

This research examined all cases of pharmacist misconduct sourced from the Health Practitioners Disciplinary Tribunal (HPDT) database in New Zealand since 2004. Characteristics of the sampled pharmacists and cases were extracted, followed by a systematic coding of the observed misconduct issues. Identification of risk factors was accomplished through content analysis techniques, enabling an assessment of their prevalence across various forms of misconduct.

Results

The dataset of pharmacist misconduct cases comprised 58 disciplinary records involving 55 pharmacists. Seven types of misconduct were identified, with the most commonly observed being quality and safety issues related to drug, medication and care, as well as criminal conviction. A total of 13 risk factors were identified and systematically classified into three categories: (1) social, regulatory, and external environmental factors, (2) systematic, organisational, and practical considerations in the pharmacy, and (3) pharmacist individual factors. The most frequently mentioned and far-reaching factors include busyness, heavy workload or distraction; health impairment issues; and life stress or challenges.

Conclusions

The patterns of pharmacist misconduct are complicated, multifaceted, and involve complex interactions among risk factors. Collaborative efforts involving individual pharmacists, professional bodies, responsible authorities, policy-makers, health funders and planners in key areas such as pharmacist workload and well-being are expected to mitigate the occurrence of misconduct. Future research should seek to uncover the origins, manifestations, and underlying relationships of various contributing factors through empirical research with appropriate individuals.
The distribution structure of medical and care resources based on regional characteristics throughout Japan in 2020
Authors: Kusunoki Takuya , Yoshikawa Tohru
Published: February 2024

Background

Given Japan’s rapidly aging population, the Ministry of Health, Labour and Welfare's policy of reducing hospital beds and replacing medical care with nursing care requires the establishment of a coordinated system of medical and care services tailored to regional characteristics. To gain useful knowledge for the development of such a system, this study aimed to identify differences in the structure of the relationship between medical and care resources due to differences in regional characteristics.

Methods

Initially, regional characteristics were used to group all 334 secondary medical areas (SMA) in Japan by principal component analysis. Subsequently, the related structure of the distribution of medical and care resources for each group were compared. For these　comparisons, first, the related structure of the distribution of medical and care resources nationwide was modeled using structural equation modeling. Secondly, multigroup analysis was conducted to investigate differences among the models across groups.

Results

The nationwide SMAs were grouped largely based on urbanicity and middle-density regionality. The groups with high urbanicity and high middle-density regionality consisted of SMAs with a high and medium population density. By contrast, the low middle-density regionality group consisted of SMAs containing large cities with a high population density and depopulated areas with a low population density. The model of the related structure of the distribution of medical and care resources differed among these groups. In the non-urbanicity and middle-density regionality groups, nursing care abundance tended to increase acute care abundance. In addition, in all groups, nursing care abundance tended to increase long-term hospitalization care abundance and clinic care abundance (with beds).

Conclusions

The key finding of this study was that the government’s objective of reducing hospital beds may not be achieved solely by expanding nursing homes. This is because many of the models did not show a tendency that higher nursing care abundance reduces the values of the factors which increase more hospital beds. This finding was particularly relevant in middle-density regionality groups. This finding suggests that the location of nursing homes should be monitored because of concerns about the oversupply of nursing homes and sprawl in those areas.
Genetic investigation into the broad health implications of caffeine: evidence from phenome-wide, proteome-wide and metabolome-wide Mendelian randomization
Authors: Zagkos Loukas , Cronjé Héléne T. , Woolf Benjamin , de La Harpe Roxane , Burgess Stephen , Mantzoros Christos S. , Elliott Paul , Yuan Shuai , Larsson Susanna C. , Tzoulaki Ioanna , Gill Dipender
Published: February 2024

Background

Caffeine is one of the most utilized drugs in the world, yet its clinical effects are not fully understood. Circulating caffeine levels are influenced by the interplay between consumption behaviour and metabolism. This study aimed to investigate the effects of circulating caffeine levels by considering genetically predicted variation in caffeine metabolism.

Methods

Leveraging genetic variants related to caffeine metabolism that affect its circulating levels, we investigated the clinical effects of plasma caffeine in a phenome-wide association study (PheWAS). We validated novel findings using a two-sample Mendelian randomization framework and explored the potential mechanisms underlying these effects in proteome-wide and metabolome-wide Mendelian randomization.

Results

Higher levels of genetically predicted circulating caffeine among caffeine consumers were associated with a lower risk of obesity (odds ratio (OR) per standard deviation increase in caffeine = 0.97, 95% confidence interval (CI) CI: 0.95—0.98, p = 2.47 × 10−4), osteoarthrosis (OR = 0.97, 95% CI: 0.96—0.98, P=1.10 × 10−8) and osteoarthritis (OR: 0.97, 95% CI: 0.96 to 0.98, P = 1.09 × 10−6). Approximately one third of the protective effect of plasma caffeine on osteoarthritis risk was estimated to be mediated through lower bodyweight. Proteomic and metabolomic perturbations indicated lower chronic inflammation, improved lipid profiles, and altered protein and glycogen metabolism as potential biological mechanisms underlying these effects.

Conclusions

We report novel evidence suggesting that long-term increases in circulating caffeine may reduce bodyweight and the risk of osteoarthrosis and osteoarthritis. We confirm prior genetic evidence of a protective effect of plasma caffeine on risk of overweight and obesity. Further clinical study is warranted to understand the translational relevance of these findings before clinical practice or lifestyle interventions related to caffeine consumption are introduced.
Safety, feasibility, and impact on the gut microbiome of kefir administration in critically ill adults
Authors: Gupta Vinod K. , Rajendraprasad Sanu , Ozkan Mahmut , Ramachandran Dhanya , Ahmad Sumera , Bakken Johan S. , Laudanski Krzysztof , Gajic Ognjen , Bauer Brent , Zec Simon , Freeman David W. , Khanna Sahil , Shah Aditya , Skalski Joseph H. , Sung Jaeyun , Karnatovskaia Lioudmila V.
Published: February 2024

Background

Dysbiosis of the gut microbiome is frequent in the intensive care unit (ICU), potentially leading to a heightened risk of nosocomial infections. Enhancing the gut microbiome has been proposed as a strategic approach to mitigate potential adverse outcomes. While prior research on select probiotic supplements has not successfully shown to improve gut microbial diversity, fermented foods offer a promising alternative. In this open-label phase I safety and feasibility study, we examined the safety and feasibility of kefir as an initial step towards utilizing fermented foods to mitigate gut dysbiosis in critically ill patients.

Methods

We administered kefir in escalating doses (60 mL, followed by 120 mL after 12 h, then 240 mL daily) to 54 critically ill patients with an intact gastrointestinal tract. To evaluate kefir’s safety, we monitored for gastrointestinal symptoms. Feasibility was determined by whether patients received a minimum of 75% of their assigned kefir doses. To assess changes in the gut microbiome composition following kefir administration, we collected two stool samples from 13 patients: one within 72 h of admission to the ICU and another at least 72 h after the first stool sample.

Results

After administering kefir, none of the 54 critically ill patients exhibited signs of kefir-related bacteremia. No side effects like bloating, vomiting, or aspiration were noted, except for diarrhea in two patients concurrently on laxatives. Out of the 393 kefir doses prescribed for all participants, 359 (91%) were successfully administered. We were able to collect an initial stool sample from 29 (54%) patients and a follow-up sample from 13 (24%) patients. Analysis of the 26 paired samples revealed no increase in gut microbial α-diversity between the two timepoints. However, there was a significant improvement in the Gut Microbiome Wellness Index (GMWI) by the second timepoint (P = 0.034, one-sided Wilcoxon signed-rank test); this finding supports our hypothesis that kefir administration can improve gut health in critically ill patients. Additionally, the known microbial species in kefir were found to exhibit varying levels of engraftment in patients’ guts.

Conclusions

Providing kefir to critically ill individuals is safe and feasible. Our findings warrant a larger evaluation of kefir’s safety, tolerability, and impact on gut microbiome dysbiosis in patients admitted to the ICU.

Trial registration

NCT05416814; trial registered on June 13, 2022.
COVID-19 death risk predictors in Brazil using survival tree analysis: a retrospective cohort from 2020 to 2022
Authors: Martins Neto Carlos , Branco Maria dos Remédios Freitas Carvalho , dos Santos Alcione Miranda , de Oliveira Bruno Luciano Carneiro Alves
Published: February 2024

Purpose

This study analyses the survival of hospitalized patients with Severe Acute Respiratory Syndrome (SARS) due to COVID-19 and identifies the risk groups for death due to COVID-19 from the identification of potential interactions between its predictors.

Methods

This was a retrospective longitudinal study with data from 1,756,917 patients reported in the Influenza Epidemiological Surveillance Information System from 26 February 2020 to 31 December 2022. In this study, all adult and older (≥ 20 years) patients were hospitalized with SARS due to COVID-19, with death as the outcome. Survival tree analysis was used to identify potential interactions between the predictors. A model was built for each year of study.

Results

Hospital lethalitywas 33.2%. The worst survival curve was observed among those who underwent invasive mechanical ventilation and were aged 80 years or older in the three years of the pandemic. Black and brown race/color were predictors of deaths in the years 2020 and 2021 when there was greater demand from the health system due to the greater number of cases.

Conclusion

By applying survival tree analysis we identified several numbers of homogeneous subgroups with different risks for mortality from COVID-19. These findings show the effects of wide inequalities of access by the population, requiring effective policies for the reduction and adequate management of the disease.
The co-production process of an assessment programme: Between clarifying identity and developing the quality of French-speaking Belgian community health centres
Authors: Capiau Madeleine , Macq Jean , Thunus Sophie
Published: February 2024

Background

The assessment of primary care organizations is considered to be essential for improving care. However, the assessments’ acceptability to professionals poses a challenge. Developing assessment programmes in collaboration with the end-users is a strategy that is widely encouraged to make interventions better targeted. By doing so, it can help to prevent resistance and encourage adherence to the assessment. This process, however, is rarely reported. This paper aims to fill this gap by describing the process of the co-production of an assessment programme for community health centres (CHCs) affiliated to the Federation of Community Health Centres (FCHC) in French-speaking Belgium.

Methods

We conducted a documentary study on the co-production of the assessment programme before carrying out semi-structured interviews with the stakeholders involved in its development.

Results

CHCs in French-speaking Belgium are increasing in number and are becoming more diverse. For the FCHC, this growth and diversification pose challenges for the meaning of CHC (an identity challenge) and what beneficiaries can expect in terms of the quality of organizations declaring themselves CHC (a quality challenge). Faced with this double challenge, the FCHC decided to develop an assessment programme, initially called Label, using participatory action research. During the co-production process, this initial programme version was abandoned in favour of a new name “DEQuaP”. This new name embodies new objectives and new design regarding the assessment programme. When studying the co-production process, we attributed these changes to two controversies. The first concerns how much and which type of variety is desired among CHCs part of the FCHC. The second concerns the organization of the FCHC in its capacity as a federation. It shed light on tensions between two professional segments that, in this paper, we called “political professionalism” and “pragmatic professionalism”.

Conclusions

These controversies show the importance of underlying challenges behind the development of an assessment programme for CHCs. This provided information about the evolution of the identity of multidisciplinary organizations in primary care. Issues raised in the development of this assessment programme also show the importance of considering assessment methods that reflect and embody the current realities of these organizations and the way of developing these assessment methods.
Crosstalk between KDEL receptor and EGF receptor mediates cell proliferation and migration via STAT3 signaling
Authors: Jia Jie , Zhu Lianhui , Yue Xihua , Tang Shuocheng , Jing Shuaiyang , Tan Chuanting , Du Yulei , Gao Jingkai , Lee Intaek , Qian Yi
Published: February 2024

Hostile microenvironment of cancer cells provoke a stressful condition for endoplasmic reticulum (ER) and stimulate the expression and secretion of ER chaperones, leading to tumorigenic effects. However, the molecular mechanism underlying these effects is largely unknown. In this study, we reveal that the last four residues of ER chaperones, which are recognized by KDEL receptor (KDELR), is required for cell proliferation and migration induced by secreted chaperones. By combining proximity-based mass spectrometry analysis, split venus imaging and membrane yeast two hybrid assay, we present that EGF receptor (EGFR) may be a co-receptor for KDELR on the surface. Prior to ligand addition, KDELR spontaneously oligomerizes and constantly undergoes recycling near the plasma membrane. Upon KDEL ligand binding, the interactions of KDELR with itself and with EGFR increase rapidly, leading to augmented internalization of KDELR and tyrosine phosphorylation in the C-terminus of EGFR. STAT3, which binds the phosphorylated tyrosine motif on EGFR, is subsequently activated by EGFR and mediates cell growth and migration. Taken together, our results suggest that KDELR serves as a bona fide cell surface receptor for secreted ER chaperones and transactivates EGFR-STAT3 signaling pathway.
An angel or a devil? Current view on the role of CD8+ T cells in the pathogenesis of myasthenia gravis
Authors: Peng Yong , Yang Huan , Chen Quan , Jin Hong , Xue Ya-hui , Du Miao-qiao , Liu Shu , Yao Shun-yu
Published: February 2024

Background

Myasthenia gravis (MG) and the experimental autoimmune MG (EAMG) animal model are characterized by T-cell-induced and B-cell-dominated autoimmune diseases that affect the neuromuscular junction. Several subtypes of CD4+ T cells, including T helper (Th) 17 cells, follicular Th cells, and regulatory T cells (Tregs), contribute to the pathogenesis of MG. However, increasing evidence suggests that CD8+ T cells also play a critical role in the pathogenesis and treatment of MG.

Main body

Herein, we review the literature on CD8+ T cells in MG, focusing on their potential effector and regulatory roles, as well as on relevant evidence (peripheral, in situ, cerebrospinal fluid, and under different treatments), T-cell receptor usage, cytokine and chemokine expression, cell marker expression, and Treg, Tc17, CD3+CD8+CD20+ T, and CXCR5+ CD8+ T cells.

Conclusions

Further studies on CD8+ T cells in MG are necessary to determine, among others, the real pattern of the Vβ gene usage of autoantigen-specific CD8+ cells in patients with MG, real images of the physiology and function of autoantigen-specific CD8+ cells from MG/EAMG, and the subset of autoantigen-specific CD8+ cells (Tc1, Tc17, and IL-17+IFN-γ+CD8+ T cells). There are many reports of CD20-expressing T (or CD20 + T) and CXCR5+ CD8 T cells on autoimmune diseases, especially on multiple sclerosis and rheumatoid arthritis. Unfortunately, up to now, there has been no report on these T cells on MG, which might be a good direction for future studies.
Clinical data mining: challenges, opportunities, and recommendations for translational applications
Authors: Qiao Huimin , Chen Yijing , Qian Changshun , Guo You
Published: February 2024

Clinical data mining of predictive models offers significant advantages for re-evaluating and leveraging large amounts of complex clinical real-world data and experimental comparison data for tasks such as risk stratification, diagnosis, classification, and survival prediction. However, its translational application is still limited. One challenge is that the proposed clinical requirements and data mining are not synchronized. Additionally, the exotic predictions of data mining are difficult to apply directly in local medical institutions. Hence, it is necessary to incisively review the translational application of clinical data mining, providing an analytical workflow for developing and validating prediction models to ensure the scientific validity of analytic workflows in response to clinical questions. This review systematically revisits the purpose, process, and principles of clinical data mining and discusses the key causes contributing to the detachment from practice and the misuse of model verification in developing predictive models for research. Based on this, we propose a niche-targeting framework of four principles: Clinical Contextual, Subgroup-Oriented, Confounder- and False Positive-Controlled (CSCF), to provide guidance for clinical data mining prior to the model's development in clinical settings. Eventually, it is hoped that this review can help guide future research and develop personalized predictive models to achieve the goal of discovering subgroups with varied remedial benefits or risks and ensuring that precision medicine can deliver its full potential.
Efficacy of natural products on premature ovarian failure: a systematic review and meta-analysis of preclinical studies
Authors: Hu Hangqi , Zhang Jiacheng , Xin Xiyan , Jin Yuxin , Zhu Yutian , Zhang Haolin , Fan Ruiwen , Ye Yang , Li Dong
Published: February 2024

Objective

This study aims to investigate the effects of natural products on animal models of premature ovarian failure (POF).

Methods

We conducted comprehensive literature searches and identified relevant studies that examined the protective effects of natural products on experimental POF. We extracted quantitative data on various aspects such as follicular development, ovarian function, physical indicators, oxidative stress markers, inflammatory factors, and protein changes. The data was analyzed using random-effects meta-analyses, calculating pooled standardized mean differences and 95% confidence intervals. Heterogeneity was assessed using the I2 statistic, and bias was estimated using the SYRCLE tool.

Results

Among the 879 reviewed records, 25 articles met our inclusion criteria. These findings demonstrate that treatment with different phytochemicals and marine natural products (flavonoids, phenols, peptides, and alkaloids, etc.) significantly improved various aspects of ovarian function compared to control groups. The treatment led to an increase in follicle count at different stages, elevated levels of key hormones, and a decrease in atretic follicles and hormone levels associated with POF. This therapy also reduced oxidative stress (specifically polyphenols, resveratrol) and apoptotic cell death (particularly flavonoids, chrysin) in ovarian granulosa cells, although it showed no significant impact on inflammatory responses. The certainty of evidence supporting these findings ranged from low to moderate.

Conclusions

Phytochemicals and marine natural product therapy (explicitly flavonoids, phenols, peptides, and alkaloids) has shown potential in enhancing folliculogenesis and improving ovarian function in animal models of POF. These findings provide promising strategies to protect ovarian reserve and reproductive health. Targeting oxidative stress and apoptosis pathways may be the underlying mechanism.
Undetectable off-target effects induced by FokI catalytic domain in mouse embryos
Authors: Xie Long , Feng Hu , Li Zhifang , Li Di , Yang Xiali , Yuan Tanglong , Yan Nana , He Chenfei , Zheng Jitan , Zuo Zhenrui , Zheng Yaxuan , Cao Yaqi , Lu Yangqing , Xiong Xing Yao , Zuo Erwei
Published: February 2024

The FokI catalytic domain can be fused to various DNA binding architectures to improve the precision of genome editing tools. However, evaluation of off-target effects is essential for developing these tools. We use Genome-wide Off-target analysis by Two-cell embryo Injection (GOTI) to detect low-frequency off-target editing events in mouse embryos injected with FokI-based architectures. Specifically, we test FokI-heterodimers fused with TALENs, FokI homodimers fused with RYdCas9, or FokI catalytic domains alone resulting in no significant off-target effects. These FokI genome editing systems exhibit undetectable off-target effects in mouse embryos, supporting the further development of these systems for clinical applications.
Can absence of cardiac activity on point-of-care echocardiography predict death in out-of-hospital cardiac arrest? A systematic review and meta-analysis
Authors: Albaroudi Omar , Albaroudi Bilal , Haddad Mahmoud , Abdle-Rahman Manar E. , Kumar Thirumoothy Samy Suresh , Jarman Robert David , Harris Tim
Published: February 2024

Aim

The purpose of this systematic review and meta-analysis was to evaluate the accuracy of the absence of cardiac motion on point-of-care echocardiography (PCE) in predicting termination of resuscitation (TOR), short-term death (STD), and long-term death (LTD), in adult patients with cardiac arrest of all etiologies in out-of-hospital and emergency department setting.

Methods

A systematic review and meta-analysis was conducted based on PRISMA guidelines. A literature search in Medline, EMBASE, Cochrane, WHO registry, and ClinicalTrials.gov was performed from inspection to August 2022. Risk of bias was evaluated using QUADAS-2 tool. Meta-analysis was divided into medical cardiac arrest (MCA) and traumatic cardiac arrest (TCA). Sensitivity and specificity were calculated using bivariate random-effects, and heterogeneity was analyzed using I2 statistic.

Results

A total of 27 studies (3657 patients) were included in systematic review. There was a substantial variation in methodologies across the studies, with notable difference in inclusion criteria, PCE timing, and cardiac activity definition. In MCA (15 studies, 2239 patients), the absence of cardiac activity on PCE had a sensitivity of 72% [95% CI 62–80%] and specificity of 80% [95% CI 58–92%] to predict LTD. Although the low numbers of studies in TCA preluded meta-analysis, all patients who lacked cardiac activity on PCE eventually died.

Conclusions

The absence of cardiac motion on PCE for MCA predicts higher likelihood of death but does not have sufficient accuracy to be used as a stand-alone tool to terminate resuscitation. In TCA, the absence of cardiac activity is associated with 100% mortality rate, but low number of patients requires further studies to validate this finding. Future work would benefit from a standardized protocol for PCE timing and agreement on cardiac activity definition.
An application of decision theory on the approximation of a generalized Apollonius-type quadratic functional equation
Authors: Ahadi Azam , Saadati Reza , Allahviranloo Tofigh , O’Regan Donal
Published: February 2024

To make better decisions on approximation, we may need to increase reliable and useful information on different aspects of approximation. To enhance information about the quality and certainty of approximating the solution of an Apollonius-type quadratic functional equation, we need to measure both the quality and the certainty of the approximation and the maximum errors. To measure the quality of it, we use fuzzy sets, and to achieve its certainty, we use the probability distribution function. To formulate the above problem, we apply the concept of Z-numbers and introduce a special matrix of the form $\mathrm{diag}(A, B, C)$
diag
(
A
,
B
,
C
)
(named the generalized Z-number) where A is a fuzzy time-stamped set, B is the probability distribution function, and C is a degree of reliability of A that is described as a value of $A\ast B$
A
∗
B
. Using generalized Z-numbers, we define a novel control function to investigate H–U–R stability to approximate the solution of an Apollonius-type quadratic functional equation with quality and certainty of the approximation.
Approximation with Szász-Chlodowsky operators employing general-Appell polynomials
Authors: Raza Nusrat , Kumar Manoj , Mursaleen M.
Published: February 2024

This article explores a Chlodowsky-type extension of Szász operators using the general-Appell polynomials. The convergence properties of these operators are established by employing the universal Korovkin-type property, and the order of approximation is determined using the classical modulus of continuity. Additionally, the weighted $\mathfrak{B}$
B
-statistical convergence and statistically weighted $\mathfrak{B}$
B
-summability properties of the operators are derived. Theoretical results are supported by numerical and graphical examples.
Analysis of relevant factors influencing size of breast abscess cavity during lactation: a cross-sectional study
Authors: Yajun Gao , Yan Zou , Yi Zhang , si Chen , yan Li , Songtao Ding
Published: February 2024

Objective

The aim of this study was to investigate risk factors for the severity of breast abscess during lactation.

Methods

A cross-sectional study was conducted using data from the Questionnaire survey of breast abscess patients. According to whether the maximum abscess diameter > 5 cm, the patients were divided into two groups for univariate and multivariate regression analysis.

Results

1805 valid questionnaires were included. Univariate and Binary logistic regression analysis demonstrated that low education (OR = 1.5, 95% CI 1.1–2.0, P = 0.005), non-exclusive breastfeeding (OR = 0.7, 95% CI 0.6–0.9, P = 0.004), fever > 37.5 ℃ (OR = 0.7, 95% CI 0.6–0.9, P = 0.003), flat or inverted nipples (OR = 0.7, 95% CI 0.6–0.9, P = 0.005), antibiotic used (OR = 0.7, 95% CI 0.6–0.9, P = 0.006), and non-medical massage (OR = 0.3, 95% CI 0.2–0.4, P < 0.001) were the effective independent influencing factors for the maximum breast abscess diameter > 5 cm.

Conclusion

Low education, non-exclusive breastfeeding, fever > 37.5 ℃, inverted or flat nipples, antibiotic used, and non-medical massage history have adverse effects on the severity of breast abscess during lactation.
Integrated modelling of the determinants of household food insecurity during the 2020–2021 COVID-19 lockdown in Uganda
Authors: Semakula Henry Musoke , Liang Song , McKune Sarah Lindley , Mukwaya Paul Isolo , Mugagga Frank , Nseka Denis , Wasswa Hannington , Kayima Patrick , Achuu Simon Peter , Mwendwa Patrick , Nakato Jovia
Published: February 2024

Background

The determinants of household food insecurity (HFI) do not act in isolation, and are known to be complex, stochastic, nonlinear, and multidimensional. Despite this being especially true in periods of shocks, studies that focus on integrated modelling of the HFI determinants during the COVID-19 lockdown are scarce, with no available evidence on Uganda. The main objective of this study was to develop Bayesian belief network (BBN) models to analyse, rank, and illustrate the conceptual reasoning, and complex causal relationships among the determinants of HFI during the COVID-19 lockdown. This study was based on seven rounds of Uganda’s High-Frequency Phone Surveys data sets collected during the lockdown. A total of 15,032 households, 17 independent determinants of HFI, and 8 food security indicators were used in this study. Metrics of sensitivity, and prediction performance were used to evaluate models’ accuracy.

Results

Eight BBN models were developed for each food insecurity indicator. The accuracy rates of the models ranged between 70.5% and 93.5%, with an average accuracy rate of 78.5%, indicating excellent predictive performance in identifying the determinants of HFI correctly. Our results revealed that approximately 42.2% of the sampled households (n = 15,032) in Uganda were worried about not having enough food. An estimated 25.2% of the respondents reported skipping a meal, while 32.1% reported consuming less food. Less than 20% of the households experienced food shortage, hunger, or having nothing to eat. Overall, 30.6% of the households were food insecure during the lockdown. The top five ranked determinants of HFI were identified as follows: (1) households’ inability to produce enough food; (2) households’ inability to buy food; (3) reduced household income; (4) limited cash assistance, and (5) households’ inability to stock adequate food supplies.

Conclusions

Ranking, rather than the statistical significance of the determinants of HFI, is crucial as an approach to applied research, as it helps stakeholders determine how to allocate resources for targeted interventions within the constraints of limited funding. These findings emphasize the importance of intervening on the most highly ranked determinants of HFI to enhance the resilience of local food systems, and households’ capacity to cope with recurring and unforeseen shocks.
Finding biomarkers of experience in animals
Authors: Babington Sarah , Tilbrook Alan J. , Maloney Shane K. , Fernandes Jill N. , Crowley Tamsyn M. , Ding Luoyang , Fox Archa H. , Zhang Song , Kho Elise A. , Cozzolino Daniel , Mahony Timothy J. , Blache Dominique
Published: February 2024

At a time when there is a growing public interest in animal welfare, it is critical to have objective means to assess the way that an animal experiences a situation. Objectivity is critical to ensure appropriate animal welfare outcomes. Existing behavioural, physiological, and neurobiological indicators that are used to assess animal welfare can verify the absence of extremely negative outcomes. But welfare is more than an absence of negative outcomes and an appropriate indicator should reflect the full spectrum of experience of an animal, from negative to positive. In this review, we draw from the knowledge of human biomedical science to propose a list of candidate biological markers (biomarkers) that should reflect the experiential state of non-human animals. The proposed biomarkers can be classified on their main function as endocrine, oxidative stress, non-coding molecular, and thermobiological markers. We also discuss practical challenges that must be addressed before any of these biomarkers can become useful to assess the experience of an animal in real-life.
Gut dysbiosis induces the development of depression-like behavior through abnormal synapse pruning in microglia-mediated by complement C3
Authors: Hao Wenzhi , Ma Qingyu , Wang Lu , Yuan Naijun , Gan Hua , He Liangliang , Li Xiaojuan , Huang Junqing , Chen Jiaxu
Published: February 2024

Background

Remodeling eubiosis of the gut microenvironment may contribute to preventing the occurrence and development of depression. Mounting experimental evidence has shown that complement C3 signaling is associated with the pathogenesis of depression, and disruption of the gut microbiota may be an underlying cause of complement system activation. However, the mechanism by which complement C3 participates in gut-brain crosstalk in the pathogenesis of depression remains unknown.

Results

In the present study, we found that chronic unpredictable mild stress (CUMS)-induced mice exhibited obvious depression-like behavior as well as cognitive impairment, which was associated with significant gut dysbiosis, especially enrichment of Proteobacteria and elevation of microbiota-derived lipopolysaccharides (LPS). In addition, peripheral and central complement C3 activation and central C3/CR3-mediated aberrant synaptic pruning in microglia have also been observed. Transplantation of gut microbiota from CUMS-induced depression model mice into specific pathogen-free and germ-free mice induced depression-like behavior and concomitant cognitive impairment in the recipient mice, accompanied by increased activation of the complement C3/CR3 pathway in the prefrontal cortex and abnormalities in microglia-mediated synaptic pruning. Conversely, antidepressants and fecal microbiota transplantation from antidepressant-treated donors improved depression-like behaviors and restored gut microbiome disturbances in depressed mice. Concurrently, inhibition of the complement C3/CR3 pathway, amelioration of abnormal microglia-mediated synaptic pruning, and increased expression of the synapsin and postsynaptic density protein 95 were observed. Collectively, our results revealed that gut dysbiosis induces the development of depression-like behaviors through abnormal synapse pruning in microglia-mediated by complement C3, and the inhibition of abnormal synaptic pruning is the key to targeting microbes to treat depression.

Conclusions

Our findings provide novel insights into the involvement of complement C3/CR3 signaling and aberrant synaptic pruning of chemotactic microglia in gut-brain crosstalk in the pathogenesis of depression.