bluuebunny/crossref_metadata_2025 huggingface dataset:
Paralog-specific signaling by IRAK1/4 maintains MyD88-independent functions in MDS/AML
Authors: Bennett Joshua , Ishikawa Chiharu , Agarwal Puneet , Yeung Jennifer , Sampson Avery , Uible Emma , Vick Eric , Bolanos Lyndsey C. , Hueneman Kathleen , Wunderlich Mark , Kolt Amal , Choi Kwangmin , Volk Andrew , Greis Kenneth D. , Rosenbaum Jan , Hoyt Scott B. , Thomas Craig J. , Starczynowski Daniel T.
Published: May 2023

Dysregulation of innate immune signaling is a hallmark of hematologic malignancies. Recent therapeutic efforts to subvert aberrant innate immune signaling in myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) have focused on the kinase IRAK4. IRAK4 inhibitors have achieved promising, though moderate, responses in preclinical studies and clinical trials for MDS and AML. The reasons underlying the limited responses to IRAK4 inhibitors remain unknown. In this study, we reveal that inhibiting IRAK4 in leukemic cells elicits functional complementation and compensation by its paralog, IRAK1. Using genetic approaches, we demonstrate that cotargeting IRAK1 and IRAK4 is required to suppress leukemic stem/progenitor cell (LSPC) function and induce differentiation in cell lines and patient-derived cells. Although IRAK1 and IRAK4 are presumed to function primarily downstream of the proximal adapter MyD88, we found that complementary and compensatory IRAK1 and IRAK4 dependencies in MDS/AML occur via noncanonical MyD88-independent pathways. Genomic and proteomic analyses revealed that IRAK1 and IRAK4 preserve the undifferentiated state of MDS/AML LSPCs by coordinating a network of pathways, including ones that converge on the polycomb repressive complex 2 complex and JAK-STAT signaling. To translate these findings, we implemented a structure-based design of a potent and selective dual IRAK1 and IRAK4 inhibitor KME-2780. MDS/AML cell lines and patient-derived samples showed significant suppression of LSPCs in xenograft and in vitro studies when treated with KME-2780 as compared with selective IRAK4 inhibitors. Our results provide a mechanistic basis and rationale for cotargeting IRAK1 and IRAK4 for the treatment of cancers, including MDS/AML.
A prospective study of chronic postsurgical pain in elderly patients: incidence, characteristics and risk factors
Authors: Jin Juying , Zhang Ting , Xiong Xianwei , Chen Huan , Jiang Yiling , He Shuangyu
Published: May 2023

Background

Due to the continued growth of surgical procedures in older adults and the significant impact of chronic postsurgical pain (CPSP), it is crucial to improve our understanding of the occurrence of CPSP as well as the appropriate prevention and treatment. We therefore conducted this study to determine the incidence, characteristics and risk factors of CPSP in elderly patients at both 3 and 6 months after surgery.

Methods

Elderly patients (aged ≥ 60 years) undergoing elective surgery in our institution between April 2018 and March 2020 were prospectively enrolled in this study. Data on demographics, preoperative psychological well-being, intraoperative surgical and anesthesia management, and acute postoperative pain intensity were collected. At 3 and 6 months after surgery, patients received telephone interview and completed the questionnaires regarding chronic pain characteristics, analgesic consumption, and interference of the pain with activities of daily living (ADL).

Results

A total of 1065 elderly patients were followed up for 6 postoperative months and included in final analysis. At 3 and 6 months after operation, the incidence of CPSP was 35.6% [95% confidence interval (95% CI) 32.7 − 38.8%] and 21.5% (95% CI 19.0% − 23.9%), respectively. CPSP cause negative impacts on patient’s ADL and most particularly on mood. Neuropathic features were found in 45.1% of the patients with CPSP at 3 months. At 6 months, 31.0% of those with CPSP reported that the pain had neuropathic features. Preoperative anxiety [3 months: Odds ratio (OR) 2.244, 95% CI 1.693 to 2.973; 6 months: OR 2.397, 95% CI 1.745 to 3.294], preoperative depression (3 months: OR 1.709, 95% CI 1.292 to 2.261; 6 months: OR 1.565, 95% CI 1.136–2.156), orthopedic surgery (3 months: OR 1.927, 95% CI 1.112 to 3.341; 6 months: OR 2.484, 95% CI 1.220 to 5.061), higher pain severity on movement within postoperative 24 h (3 months: OR 1.317, 95% CI 1.191 to 1.457; 6 months: OR 1.317, 95% CI 1.177 to 1.475) were associated with a higher risk for CPSP independently at both 3 and 6 months after surgery.

Conclusions

CPSP is a common postoperative complication in elderly surgical patients. Preoperative anxiety and depression, orthopedic surgery, and greater intensity of acute postoperative pain on movement are associated with an increased risk for CPSP. It should be kept in mind that developing psychological interventions to reduce anxiety and depression and optimizing the management of acute postoperative pain will be effective in reducing the development of CPSP in this population.
Loss of control eating during pregnancy is associated with excessive gestational weight gain among individuals with overweight and obesity
Authors: Levine Michele D. , Tavernier Rebecca L. Emery , Conlon Rachel P. K. , Grace Jennifer L. , Sweeny Gina M. , Wang Bang , Cheng Yu
Published: May 2023

Background

Excessive gestational weight gain (GWG) predicts negative health outcomes among individuals with overweight or obesity. Loss of control eating (LOC), the ingestion of food associated with being unable to control eating, is the core psychopathology of binge eating disorders. We evaluated the contribution of LOC to GWG among pregnant individuals with prepregnancy overweight/obesity.

Methods

In a prospective longitudinal study, individuals with prepregnancy BMI ≥ 25 (N = 257) were interviewed monthly to assess LOC and reported demographic, parity, and smoking information. GWG was abstracted from medical records.

Results

Among individuals with prepregnancy overweight/obesity, 39% endorsed LOC prior to or during pregnancy. After adjusting for factors that have previously been linked to GWG, LOC during pregnancy, uniquely predicted higher GWG and greater likelihood of exceeding GWG recommendations. Participants with prenatal LOC gained 3.14 kg (p = 0.03) more than did those without LOC during pregnancy and 78.7% (n = 48/61) exceeded IOM guidelines for GWG. The frequency of LOC episodes was also associated with greater weight gain.

Conclusions

Prenatal LOC is common among pregnant individuals with overweight/obesity and predicts greater GWG and increased likelihood of exceeding IOM GWG guidelines. LOC may represent a modifiable behavioral mechanism to prevent excessive GWG among individuals at risk for adverse pregnancy outcomes.
Changes in birth outcomes and utilization of prenatal care during the COVID-19 pandemic in 2020: a secondary analysis of vital statistics in Colombia
Authors: Guarnizo-Herreño Carol C. , Buitrago Giancarlo , Wehby George L
Published: May 2023

Background

Birth outcomes could have been affected by the COVID-19 pandemic through changes in access to prenatal services and other pathways. The aim of this study was to examine the effects of the COVID-19 pandemic on fetal death, birth weight, gestational age, number of prenatal visits, and caesarean delivery in 2020 in Colombia.

Methods

We conducted a secondary analysis of data on 3,140,010 pregnancies and 2,993,534 live births from population-based birth certificate and fetal death certificate records in Colombia between 2016 and 2020. Outcomes were compared separately for each month during 2020 with the same month in 2019 and pre-pandemic trends were examined in regression models controlling for maternal age, educational level, marital status, type of health insurance, place of residence (urban/rural), municipality of birth, and the number of pregnancies the mother has had before last pregnancy.

Results

We found some evidence for a decline in miscarriage risk in some months after the pandemic start, while there was an apparent lagging increase in stillbirth risk, although not statistically significant after correction for multiple comparisons. Birth weight increased during the onset of the pandemic, a change that does not appear to be driven by pre-pandemic trends. Specifically, mean birth weight was higher in 2020 than 2019 for births in April through December by about 12 to 21 g (p < 0.01). There was also a lower risk of gestational age at/below 37 weeks in 2020 for two months following the pandemic (April, June), but a higher risk in October. Finally, there was a decline in prenatal visits in 2020 especially in June-October, but no evidence of a change in C-section delivery.

Conclusions

The study findings suggest mixed early effects of the pandemic on perinatal outcomes and prenatal care utilization in Colombia. While there was a significant decline in prenatal visits, other factors may have had counter effects on perinatal health including an increase in birth weight on average.
Implementing an exclusive human milk diet for preterm infants: real-world experience in diverse NICUs
Authors: Swanson Jonathan R. , Becker Amy , Fox Jenny , Horgan Michael , Moores Russell , Pardalos John , Pinheiro Joaquim , Stewart Dan , Robinson Tonya
Published: May 2023

Background

Human milk–based human milk fortifier (HMB-HMF) makes it possible to provide an exclusive human milk diet (EHMD) to very low birth weight (VLBW) infants in neonatal intensive care units (NICUs). Before the introduction of HMB-HMF in 2006, NICUs relied on bovine milk–based human milk fortifiers (BMB-HMFs) when mother's own milk (MOM) or pasteurized donor human milk (PDHM) could not provide adequate nutrition. Despite evidence supporting the clinical benefits of an EHMD (such as reducing the frequency of morbidities), barriers prevent its widespread adoption, including limited health economics and outcomes data, cost concerns, and lack of standardized feeding guidelines.

Methods

Nine experts from seven institutions gathered for a virtual roundtable discussion in October 2020 to discuss the benefits and challenges to implementing an EHMD program in the NICU environment. Each center provided a review of the process of starting their program and also presented data on various neonatal and financial metrics associated with the program. Data gathered were either from their own Vermont Oxford Network outcomes or an institutional clinical database. As each center utilizes their EHMD program in slightly different populations and over different time periods, data presented was center-specific. After all presentations, the experts discussed issues within the field of neonatology that need to be addressed with regards to the utilization of an EHMD in the NICU population.

Results

Implementation of an EHMD program faces many barriers, no matter the NICU size, patient population or geographic location. Successful implementation requires a team approach (including finance and IT support) with a NICU champion. Having pre-specified target populations as well as data tracking is also helpful. Real-world experiences of NICUs with established EHMD programs show reductions in comorbidities, regardless of the institution’s size or level of care. EHMD programs also proved to be cost effective. For the NICUs that had necrotizing enterocolitis (NEC) data available, EHMD programs resulted in either a decrease or change in total (medical + surgical) NEC rate and reductions in surgical NEC. Institutions that provided cost and complications data all reported a substantial cost avoidance after EHMD implementation, ranging between $515,113 and $3,369,515 annually per institution.

Conclusions

The data provided support the initiation of EHMD programs in NICUs for very preterm infants, but there are still methodologic issues to be addressed so that guidelines can be created and all NICUs, regardless of size, can provide standardized care that benefits VLBW infants.
The role of self-efficacy and parental communication in the association between cyber victimization and depression among adolescents and young adults: a structural equation model
Authors: Maurya Chanda , Muhammad T. , Das Ayushi , Fathah Abdul , Dhillon Preeti
Published: May 2023

Background

With the rapid advancement and revolutionization of information and communication technologies, adolescents and young adults use smartphones, the internet, and social networking services more frequently, as a result, the problem of cyber-bullying sharply increases, and eventually it causes psychological issues and negative thoughts in the victims. This study aimed to examine the role of self-efficacy and parental communication in the relationship between cyber victimization and depression among adolescents and young adults in India.

Methods

Secondary data analysis was performed on a cross-sectional dataset obtained from the Understanding the Lives of Adolescents and Young Adults (UDAYA) wave 2 survey. The sample included 16,292 adolescent and young adult boys and girls aged 12–23 years. Karl Pearson Correlation coefficient analysis was done to examine the correlation between outcome variable (depressive symptoms), mediator variables (self-efficacy and parental communication) and key explanatory variable (cyber victimization). Further, structural equation modeling technique was applied to examine the hypothesized pathways.

Results

Adolescents and young adults being victims of cyber-bullying [β = 0.1357, p < 0.001] and those witnessed inter-parental violence were positively [β = 0.0026, p < 0.001] correlated with depressive symptoms. Self-efficacy and parental communication were negatively related to depressive symptoms among adolescents and young adults. There was a significant positive relationship between cyber victimization [β = 0.258, p < 0.001] and depressive symptoms. Cyber victimization was positively related to self-efficacy [β = 0.043, p < 0.001] among adolescents and young adults. Self-efficacy [β= -0.150, p < 0.001] and parental communication [β=-0.261, p < 0.001] reduced depressive symptoms among the participants.

Conclusions

The findings suggest that adolescents and young adults who are victims of cyber-bully may have depressive symptoms and their mental health can be improved through the enhancement of self-efficacy and increased parental communication. Improved peer attitudes and familial support for empowering cyber victims should be taken into account while framing programs and interventions.
Trends in the utilisation of skilled birth attendance among pregnant women in Benin, from 2001 to 2017-2018, and projections to 2030
Authors: Talon Pascaline Yvonne , Saizonou Jacques , Kpozèhouen Alphonse , Zannou Robert Franck , Ouendo Edgard-Marius
Published: May 2023

Background

Skilled birth attendance during childbirth is known to promote better pregnancy outcomes as well as contribute to maternal and newborn survival. The study aimed to analyse the progress in the use of skilled birth attendance by pregnant women over the last two decades (2001 to 2017–2018) in Benin, and then to make projections to 2030.

Methods

A secondary analysis was made using Benin's Demographic and Health Survey (DHS) databases. The study population were i) women of 15–49 years of age who were successfully surveyed and usually resided in the households visited during DHS-II, DHS-III, DHS-IV and DHS-V, ii) and had had at least one live birth in the five years preceding each of these surveys. For each DHS, the corresponding proportion of births attended by skilled health personnel was determined. The study then generated the Annual Percent Change (APC) between each survey and globally, and projections were made to 2030.

Results

Nationally, the percentage of women who gave birth attended by skilled health personnel was 67.39% in 2001, 76.10% in 2006, 80.87% in 2011–2012, and 79.12% in 2017–2018; this represents an APC = 0.98% between 2001 and 2017–2018. If the historical rate of progression is maintained, it is expected that by 2030, 89.35% of pregnant women will be using skilled birth attendance services.

Conclusion

Efforts are needed to understand the drivers of skilled birth attendance among pregnant women to adopt appropriate strategies.
Fatal, non-fatal burden of cancer in the elderly in China, 2005–2016: a nationwide registry-based study
Authors: Ma Zhen-Rong , Lin Kang-Qian , Guo Hong , Yang Kai-Yue , Cao Miao , Song Xi , Jia Huai-Miao , Hu Yun-Hua , Yan Yi-Zhong
Published: May 2023

Background

As populations age, cancer burden becomes increasingly conspicuous. This study quantified the cancer burden of the elderly (≥ 60 years) in China, based on the China Cancer Registry Annual Report to provide epidemiological evidence for cancer prevention and control.

Methods

Data on cancer cases and deaths among the elderly aged ≥ 60 years were collected from the China Cancer Registry Annual Report, 2008–2019. Potential years of life lost (PYLL) and disability-adjusted life years (DALY) were calculated to analyze fatalities and the non-fatal burden. The time trend was analyzed using the Joinpoint model.

Results

From 2005 to 2016, the PYLL rate of cancer in the elderly was stable between 45.34‰ and 47.62‰, but the DALY rate for cancer decreased at an average annual rate of 1.18% (95% CI: 0.84–1.52%). The non-fatal cancer burden in the rural elderly was higher than that of the urban elderly. Lung, gastric, liver, esophageal, and colorectal cancers were the main cancers causing the cancer burden in the elderly, and accounted for 74.3% of DALYs. The DALY rate of lung cancer in females in the 60–64 age group increased (annual percentage change [APC] = 1.14%, 95% CI: 0.10–1.82%). Female breast cancer was one of the top five cancers in the 60–64 age group, with DALY rates that also increased (APC = 2.17%, 95% CI: 1.35–3.01%). With increasing age, the burden of liver cancer decreased, while that of colorectal cancer rose.

Conclusions

From 2005 to 2016, the cancer burden in the elderly in China decreased, mainly reflected in the non-fatal burden. Female breast and liver cancer were a more serious burden in the younger elderly, while colorectal cancer burden was mainly observed in the older elderly.
Closing the gap between screening and depression prevention: a qualitative study on barriers and facilitators from the perspective of public health professionals in a school-based prevention approach
Authors: Braam Marloes W. G. , Rasing Sanne P. A. , Heijs Dewi A. M. , Lokkerbol Joran , van Bergen Diana D. , Creemers Daan H. M. , Spijker Jan
Published: May 2023

Background

The prevalence of depression has increased among adolescents in western countries. Prevention is needed to reduce the number of adolescents who experience depression and to avoid negative consequences, including suicide. Several preventive interventions are found to be promising, especially multi-modal approaches, for example combining screening and preventive intervention. However, an important bottleneck arises during the implementation of preventive intervention. Only a small percentage of adolescents who are eligible for participation actually participate in the intervention. To ensure that more adolescents can benefit from prevention, we need to close the gap between detection and preventive intervention. We investigated the barriers and facilitators from the perspective of public health professionals in screening for depressive and suicidal symptoms and depression prevention referral in a school-based setting.

Methods

We conducted 13 semi-structured interviews with public health professionals, who execute screening and depression prevention referral within the Strong Teens and Resilient Minds (STORM) approach. The interviews were recorded, transcribed verbatim, and coded in several cycles using ATLAS.ti Web.

Results

Three main themes of barriers and facilitators emerged from the interviews, namely “professional capabilities,” “organization and collaboration,” and “beliefs about depressive and suicidal symptoms and participation in prevention”. The interviews revealed that professionals do not always feel sufficiently equipped in terms of knowledge, skills and supporting networks. Consequently, they do not always feel well able to execute the process of screening and prevention referral. In addition, a lack of knowledge and support in schools and other cooperating organizationorganizations was seen to hinder the process. Last, the beliefs of public health professionals, school staff, adolescents, and parents —especially stigma and taboo—were found to make the screening and prevention referral process more challenging.

Conclusions

To further improve the process of screening and prevention referral in a school-based setting, enhancing professional competence and a holding work environment for professionals, a strong collaboration and a joint approach with schools and other cooperating organizations and society wide education about depressive and suicidal symptoms and preventive intervention are suggested. Future research should determine whether these recommendations actually lead to closing the gap between detection and prevention.
CEP55: an immune-related predictive and prognostic molecular biomarker for multiple cancers
Authors: Li Guo-Sheng , Zhang Wei , Huang Wan-Ying , He Rong-Quan , Huang Zhi-Guang , Gan Xiang-Yu , Yang Zhen , Dang Yi-Wu , Kong Jin-Liang , Zhou Hua-Fu , Chen Gang
Published: May 2023

Background

Centrosomal protein 55 (CEP55) plays a significant role in specific cancers. However, comprehensive research on CEP55 is lacking in pan-cancer.

Methods

In-house and multi-center samples (n = 15,823) were used to analyze CEP55 in 33 cancers. The variance of CEP55 expression levels among tumor and control groups was evaluated by the Wilcoxon rank-sum test and standardized mean difference (SMD). The clinical value of CEP55 in cancers was assessed using receiver operating characteristic (ROC) curves, Cox regression analysis, and Kaplan-Meier curves. The correlations between CEP55 expression and the immune microenvironment were explored using Spearman’s correlation coefficient.

Results

The data of clustered regularly interspaced short palindromic repeats confirmed that CEP55 was essential for the survival of cancer cells in multiple cancer types. Elevated CEP55 mRNA expression was observed in 20 cancers, including glioblastoma multiforme (p < 0.05). CEP55 mRNA expression made it feasible to distinguish 21 cancer types between cancer specimens and their control samples (AUC = 0.97), indicating the potential of CEP55 for predicting cancer status. Overexpression of CEP55 was correlated with the prognosis of cancer individuals for 18 cancer types, exhibiting its prognostic value. CEP55 expression was relevant to tumor mutation burden, microsatellite instability, neoantigen counts, and the immune microenvironment in various cancers (p < 0.05). The expression level and clinical relevance of CEP55 in cancers were verified in lung squamous cell carcinoma using in-house and multi-center samples (SMD = 4.07; AUC > 0.95; p < 0.05).

Conclusion

CEP55 may be an immune-related predictive and prognostic marker for multiple cancers, including lung squamous cell carcinoma.
The effect of therapeutic physical modalities on pain, function, and quality of life in patients with myofascial pain syndrome: a systematic review
Authors: He Peijue , Fu Wenxuan , Shao Hang , Zhang Meng , Xie Zhuoli , Xiao Juan , Li Lijuan , Liu Yiwei , Cheng Yi , Wang Qian
Published: May 2023

Background

Myofascial pain syndrome (MPS) is a common musculoskeletal pain and dysfunction, which is characterised by myofascial trigger points. Therapeutic physical modalities, as potentially effective treatment options, are commonly used in the clinical setting for the patients with MPS.

Objective

This systematic review aimed to evaluate the safety and effectiveness of therapeutic physical modalities in the treatment of MPS, investigate its therapeutic mechanisms and provide a scientific evidence-based decision.

Methods

According to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, the PubMed, Cochrane Central Library, Embase, and CINAHL databases were searched for randomized controlled clinical studies published from database inception to October 30, 2022. A total of 25 articles met the study inclusion criteria. Data were extracted from these studies and a qualitative analysis was performed.

Results

Transcutaneous electrical nerve stimulation therapy, extracorporeal shock wave therapy, laser therapy, and other therapeutic physical modalities have been demonstrated to improve the pain symptoms, joint mobility, psychological state, and quality of life in the patients with MPS and no side effects have been reported. The curative effect of therapeutic physical modalities was found to be possibly associated with increased blood perfusion and oxygen supply in ischaemic tissues, reduced hyperalgesia in the peripheral and central nerves, and decreased involuntary muscle contractions.

Conclusion

The systematic review has shown that therapeutic physical modalities could provide a safe and effective therapeutic option for MPS. However, the consensus is currently lacking regarding the optimal treatment paradigm, therapeutic parameters, and mutual combination of therapeutic physical modalities. The clinical trials with robust quality are required to further promote the evidence-based application of therapeutic physical modalities for MPS.
A giant invasive macroprolactinoma with recurrent nasal bleeding as the first clinical presentation: case report and review of literature
Authors: Li Danting , Wang Yan , Tan Huiwen , Luo Peiqiong , Yu Yerong
Published: May 2023

Background

Giant prolactinoma (> 4 cm in dimension) is a rare disorder. Invasive macroprolactinoma has the potential to cause base of skull erosion and extend into the nasal cavity or even the sphenoid sinus. Nasal bleeding caused by intranasal tumor extension is a rare complication associated with invasive giant prolactinoma.

We report a case of giant invasive macroprolactinoma with repeated nasal bleeding as the initial symptom.

Case presentation

A 24-year-old man with an invasive giant prolactinoma in the nasal cavity and sellar region who presented with nasal bleeding as the initial symptom, misdiagnosed as olfactory neuroblastoma. However, markedly elevated serum prolactin levels (4700 ng/mL), and a 7.8-cm invasive sellar mass confirmed the diagnosis of invasive giant prolactinoma. He was treated with oral bromocriptine. Serum prolactin was reduced to near normal after 6 months of treatment. Follow-up magnetic resonance imaging showed that the sellar lesion had disappeared completely and the skull base lesions were reduced.

Conclusion

This case is notable in demonstrating the aggressive nature of untreated invasive giant prolactinomas which can cause a diagnostic difficulty with potential serious consequences. Early detection of hormonal levels can avoid unnecessary nasal biopsy. Early identification of pituitary adenoma with nasal bleeding as the first symptom is particularly important.
Barrier analysis for continuity of palliative care from health facility to household among adult cancer patients in Addis Ababa, Ethiopia
Authors: Abate Yonas , Solomon Kalkidan , Azmera Yoseph Mamo , de Fouw Marlieke , Kaba Mirgissa
Published: May 2023

Background

Annually 57 million people across the globe require palliative care, 76% are from low- and-middle income countries. Continuity of palliative care contributes to a decline in emergency room visits., decreased hospital deaths, improved patient satisfaction, better utilization of services, and cost savings. Despite efforts made to develop the palliative care guideline in Ethiopia, the service is not yet organized and linked to primary health care. This study aimed to explore barriers to the continuum of palliative care from facility to household for cancer patients in Addis Ababa.

Methods

Qualitative exploratory study was conducted with face-to-face interviews with a total of 25 participants. The study population was adult cancer patients, primary caregivers, healthcare providers, volunteers, and nationwide advocates. Data were audio recorded, transcribed verbatim and finally imported to Open code version 4.02 software for coding and analysis. Thematic analysis was guided by Tanahashi’s framework.

Results

The key barriers to continuity of palliative care included opioid scarcity and turnover and shortage of healthcare workers. A shortfall of diagnostic materials, cost of medications, lack of government backing, and home-based center’s enrollment capacity hampered accessibility. Care providers were instruments of cultural barriers in delivering appropriate end-of-life care, on the other hand, patients’ preference for conventional medicine hindered acceptability. Lack of community volunteers, failure of health extension workers to link patients, and spatial limits fraught utilization. The lack of defined roles and services at several levels and the workload on healthcare professionals affected the effectiveness of the nexus.

Conclusion

The continuum of palliative care service from health facility to household in Ethiopia is yet in its infancy compromised by factors related to availability, accessibility, acceptability, utilization, and effectiveness. Further research is required to delineate the roles of various actors; the health sector should smudge out the continuum of palliation to cope with the growing need for palliative care.
CAR T cell-based immunotherapy and radiation therapy: potential, promises and risks
Authors: Hovhannisyan Lusine , Riether Carsten , Aebersold Daniel M. , Medová Michaela , Zimmer Yitzhak
Published: May 2023

CAR T cell-based therapies have revolutionized the treatment of hematological malignancies such as leukemia and lymphoma within the last years. In contrast to the success in hematological cancers, the treatment of solid tumors with CAR T cells is still a major challenge in the field and attempts to overcome these hurdles have not been successful yet. Radiation therapy is used for management of various malignancies for decades and its therapeutic role ranges from local therapy to a priming agent in cancer immunotherapy. Combinations of radiation with immune checkpoint inhibitors have already proven successful in clinical trials. Therefore, a combination of radiation therapy may have the potential to overcome the current limitations of CAR T cell therapy in solid tumor entities. So far, only limited research was conducted in the area of CAR T cells and radiation. In this review we will discuss the potential and risks of such a combination in the treatment of cancer patients.
‘This is hardcore’: a qualitative study exploring service users’ experiences of Heroin-Assisted Treatment (HAT) in Middlesbrough, England
Authors: Riley Fleur , Harris Magdalena , Poulter Hannah Louise , Moore Helen J. , Ahmed Daniel , Towl Graham , Walker Tammi
Published: May 2023

Background

Heroin-Assisted Treatment (HAT) is well evidenced internationally to improve health and social outcomes for people dependent on opioids who have not been helped by traditional treatment options. Despite this evidence base, England has been slow to implement HAT. The first service outside of a trial setting opened in 2019, providing twice-daily supervised injections of medical-grade heroin (diamorphine) to a select sample of high-risk heroin users in Middlesbrough. This paper explores their experiences, including the negotiation of the strict regularly controls required of a novel intervention in the UK context.

Methods

We conducted in-depth interviews with service providers and users of the Middlesbrough HAT service between September and November 2021. Data from each group were thematically analysed and reported separately. This paper details the experiences of the twelve heroin dependent men and women accessing HAT.

Results

Participants’ accounts of HAT treatment evidenced a tension between the regulatory constraints and uncertainty of treatment provision, and the positive outcomes experienced through supportive service provision and an injectable treatment option. Limited confidence was held in treatment efficacy, longevity of funding, and personal capacity for treatment success. This was counteracted by a strong motivation to cease engagement with the illicit drug market. While attendance requirements placed restrictions on daily activities, participants also experienced benefits from strong, supportive bonds built with the service providers through their continued engagement.

Conclusions

The Middlesbrough HAT programme provided benefits to a high-risk population of opioid dependent people who were unable or disinclined to participate in conventional opioid substitution treatments. The findings in this paper highlight the potential for service modifications to further enhance engagement. The closure of this programme in 2022 prohibits this opportunity for the Middlesbrough community, but holds potential to inform advocacy and innovation for future HAT interventions in England.
Sexual dimorphism of the posterior condylar offset of the femur and the medial posterior slope of the tibia in non-arthritic knees of Egyptian adults: an MRI study
Authors: Abdelnasser Mohammad Kamal , Abdelhameed Mohammed Anter , Bassem Micheal , Adam Mahmoud Faisal , Bakr Hatem M. , Khalifa Yaser E.
Published: May 2023

Background

The aim of this magnetic resonance imaging (MRI) study was to investigate controversial sexual dimorphism of the posterior condylar offset of the femur (the offset) and the posterior slope of the tibia (the slope) in non-arthritic knees of Egyptian adults.

Methods

On 100 male and 100 female MRIs of non-arthritic knees, linear measurements of the distal part of the femur (the offset) and the angular measurements of the proximal part of the tibia (the slope) were performed and compared regarding sex and ethnicity. The intraclass correlation coefficient (ICC) was used to test the interrater agreement.

Results

Both offsets and the lateral offset ratio were larger in males (p < 0.001), the medial offset ratio, and the medial slope in females (p from < 0.001 to 0.007), whereas the lateral slope was sex-free (p = 0.41). Irrespective of sex, however, the medial offset with its ratio, and the medial slope were larger than their counterparts (p < 0.001). Our means of the offsets, their ratios, and the slopes mostly differed from those of other ethnicities (p from ≤ 0.001 to 0.004). ICCs > 0.8 proved MRI’s precision was high.

Conclusion

There was a sexual dimorphism of both the offset and the medial slope in non-arthritic knees of Egyptian adults. We believe future designs of knee implants should consider these differences in order to improve postoperative range of motion and patients’ satisfaction after total knee arthroplasty.

Level of evidence Level III Retrospective Cohort Study.

Trial registrationClinicalTrials.gov identifier: NCT03622034, registered on July 28, 2018.
Modic changes as seen on MRI are associated with nonspecific chronic lower back pain and disability
Authors: Czaplewski Lloyd G. , Rimmer Otis , McHale Duncan , Laslett Mark
Published: May 2023

Background

Estimating the contribution of endplate oedema known as Modic changes to lower back pain (LBP) has been the subject of multiple observational studies and reviews, some of which conclude that the evidence for an association of Modic change with LBP is uncertain while others demonstrate a clear link. The clinical trials demonstrating the benefit of basivertebral nerve ablation, a therapeutic intervention, in a tightly defined homogenous patient group with chronic LBP and Modic changes type 1 or type 2, provides further evidence for the contribution of Modic changes to LBP and shows that in these subjects, nerve ablation substantially reduces pain and disability. These interventional studies provide direct evidence that Modic changes can be associated with lower back pain and disability. This review set out to explore why the literature to date has been conflicting.

Methods

A narrative, forensic, non-systematic literature review of selected articles to investigate why the published literature investigating the association between Modic imaging changes and chronic low back pain is inconsistent.

Results

This review found that previous systematic reviews and meta-analyses included both heterogeneous study designs and diverse patient syndromes resulting in an inconsistent association between Modic changes and nonspecific chronic lower back pain. Re-analysis of literature data focussing on more homogenous patient populations provides clearer evidence that Modic changes are associated with nonspecific chronic lower back pain and that type 1 Modic changes are more painful than type 2.

Conclusions

Studies using tightly defined homogenous patient groups may provide the best test for association between MRI-findings and pain and disability. Clinical benefit of basivertebral nerve ablation observed in randomised controlled trials further supports the association between type 1 and type 2 Modic changes with pain and disability.
Is the construct stability of the acetabular cup affected by the acetabular screw configuration in bone defect models?
Authors: Nam Ho-Jin , Lim Young-Wook , Jo Woo-Lam , Bahk Ji Hoon , Kwon Soon-Yong , Park Hyung Chul , AlShammari Saad Mohammed
Published: May 2023

Background

In revision surgery with significant segmental acetabular defects, adequate implant selection and fixation methods are critical in determining successful bony ingrowth. Commercially available total hip prosthesis manufacturers generally offer additional multi-hole options of acetabular shells with identical designs for use in revision THAs where screw holes configurations vary from product to product. This study aims to compare the mechanical stability of the two types of acetabular screw constructs for the fixation of acetabular components: spread-out and pelvic brim-focused configurations.

Methods

We prepared 40 synthetic bone models of the male pelvis. In half of the samples with acetabular defects, identical curvilinear bone defects were manually created using an oscillating electrical saw. On the right side, multi-hole-cups in which the direction of the screw holes are centered on the pelvic brim (brim-focused) and, on the left side, multi-hole-cups with the direction of the screw hole spread throughout the acetabulum (spread-out) were implanted into the pelvic synthetic bones. Coronal lever-out and axial torsion tests were performed with a testing machine, measuring load versus displacement.

Results

The average torsional strengths were significantly higher in the spread-out group over the brim-focused group regardless of the presence of the segmental defect of the acetabulum (p < 0.001). But for the lever-out strength, the spread-out group exhibited significantly higher average strength over the brim-focused group for the intact acetabulum (p = 0.004), whereas the results were reversed in the brim-focused group when the defects were generated (p < 0.001). The presence of acetabular defects reduced the average torsional strengths of the two groups by 68.66% versus 70.86%. In comparison, the decrease in the average lever-out strength was less significant for the brim-focused group than the spread-out group (19.87% vs. 34.25%) (p < 0.001).

Conclusion

Constructs of multi-hole acetabular cups with the spread-out screw holes configuration exhibited statistically better axial torsional strength and coronal lever-out strength. With the presence of posterior segmental bone defects, the spread-out constructs demonstrated significantly better tolerance to axial torsional strength. Still, they exhibited inverted results of higher lever-out strength in the pelvic brim-focused constructs.
Genetic basis of geographical differentiation and breeding selection for wheat plant architecture traits
Authors: Liu Yangyang , Shen Kuocheng , Yin Changbin , Xu Xiaowan , Yu Xuchang , Ye Botao , Sun Zhiwen , Dong Jiayu , Bi Aoyue , Zhao Xuebo , Xu Daxing , He Zhonghu , Zhang Xueyong , Hao Chenyang , Wu Jianhui , Wang Ziying , Wu He , Liu Danni , Zhang Lili , Shen Liping , Hao Yuanfeng , Lu Fei , Guo Zifeng
Published: May 2023

Background

Plant architecture associated with increased grain yield and adaptation to the local environments is selected during wheat (Triticum aestivum) breeding. The internode length of individual stems and tiller length of individual plants are important for the determination of plant architecture. However, few studies have explored the genetic basis of these traits.

Results

Here, we conduct a genome-wide association study (GWAS) to dissect the genetic basis of geographical differentiation of these traits in 306 worldwide wheat accessions including both landraces and traditional varieties. We determine the changes of haplotypes for the associated genomic regions in frequency in 831 wheat accessions that are either introduced from other countries or developed in China from last two decades. We identify 83 loci that are associated with one trait, while the remaining 247 loci are pleiotropic. We also find 163 associated loci are under strong selective sweep. GWAS results demonstrate independent regulation of internode length of individual stems and consistent regulation of tiller length of individual plants. This makes it possible to obtain ideal haplotype combinations of the length of four internodes. We also find that the geographical distribution of the haplotypes explains the observed differences in internode length among the worldwide wheat accessions.

Conclusion

This study provides insights into the genetic basis of plant architecture. It will facilitate gene functional analysis and molecular design of plant architecture for breeding.
Decoding enhancer complexity with machine learning and high-throughput discovery
Authors: Smith Gabrielle D. , Ching Wan Hern , Cornejo-Páramo Paola , Wong Emily S.
Published: May 2023

Enhancers are genomic DNA elements controlling spatiotemporal gene expression. Their flexible organization and functional redundancies make deciphering their sequence-function relationships challenging. This article provides an overview of the current understanding of enhancer organization and evolution, with an emphasis on factors that influence these relationships. Technological advancements, particularly in machine learning and synthetic biology, are discussed in light of how they provide new ways to understand this complexity. Exciting opportunities lie ahead as we continue to unravel the intricacies of enhancer function.
Clinical characteristics and survival of pulmonary arterial hypertension with or without interstitial lung disease in systemic sclerosis
Authors: Fairley Jessica L. , Hansen Dylan , Ross Laura , Proudman Susanna , Sahhar Joanne , Ngian Gene-Siew , Walker Jennifer , Host Lauren V. , Morrisroe Kathleen , Apostolopoulous Diane , Ferdowsi Nava , Wilson Michelle , Tabesh Maryam , Stevens Wendy , Nikpour Mandana ,   Australian Scleroderma Interest Group, Cooley Helen , Croyle Lucy , Hill Catherine , Host Lauren , Lester Sue , Major Gabor , Nash Peter , Rischmueller Maureen , Roddy Janet , Strickland Gemma , Tay Tien , Tymms Kathleen , Youssef Peter
Published: May 2023

Objectives

To describe the clinical phenotype and prognosis of people in the Australian Scleroderma (SSc) Cohort Study with pulmonary arterial hypertension (PAH) with or without interstitial lung disease (ILD).

Methods

Participants meeting ACR/EULAR criteria for SSc were divided into four mutually exclusive groups: those meeting criteria for PAH (PAH-only), ILD (ILD-only), concurrent PAH and ILD (PAH-ILD) or neither PAH nor ILD (SSc-only). Logistic or linear regression analyses were used for associations between clinical features, health-related quality of life (HRQoL) and physical function. Survival analysis was performed using Kaplan–Meier estimates and Cox-regression modelling.

Results

Of 1561 participants, 7% fulfilled criteria for PAH-only, 24% ILD-only, 7% PAH-ILD and 62% SSc-only. People with PAH-ILD were more frequently male, with diffuse skin involvement, higher inflammatory markers, older age of SSc onset and higher frequency of extensive ILD than the cohort overall (p < 0.001). People of Asian race more frequently developed PAH-ILD (p < 0.001). People with PAH-ILD or PAH-only had worse WHO functional class and 6-min-walk-distance than ILD-only (p < 0.001). HRQoL scores were worst in those with PAH-ILD (p < 0.001).

Survival was reduced in the PAH-only and PAH-ILD groups (p < 0.01). Multivariable hazard modelling demonstrated the worst prognosis in extensive ILD and PAH (HR = 5.65 95% CI 3.50–9.12 p < 0.01), followed by PAH-only (HR = 4.21 95% CI 2.89–6.13 p < 0.01) and PAH with limited ILD (HR = 2.46 95% CI 1.52–3.99 p < 0.01).

Conclusions

The prevalence of concurrent PAH-ILD in the ASCS is 7%, with poorer survival in those patients with PAH-ILD compared to ILD or SSc alone. The presence of PAH confers a poorer overall prognosis than even extensive ILD; however, further data are required to better understand the clinical outcomes of this high-risk patient group.
Cervical and ocular vestibular evoked myogenic potentials in patients with Diabetic Peripheral Neuropathy
Authors: Zhang Jinying , Ye Lichao , Bai Xuefeng , Huang Yali , Lin Jiayu , Huang Huapin
Published: May 2023

Background

Diabetes causes impaired microarterial blood flow, demyelination and neuronal damage, which may lead to cochlear damage and vestibular malfunction. Vestibular evoked myogenic potentials (VEMP) is a simple, reproducible test. Cervical and ocular vestibular evoked myogenic potentials (cVEMP and oVEMP) can be explored in the saccadic-spinal and utriculo-ocular pathways in regular clinical practice.

Objective

To evaluate possible vestibular evoked myogenic potential (VEMP) abnormalities in patients with diabetic peripheral neuropathy.

Materials and methods

89 patients with Type 2 Diabetes in the present study consisted of three groups: 29 patients with no peripheral neuropathy (NDPN group), 26 patients with asymptomatic neuropathy (SDPN group), 34 patients with symptomatic neuropathy (DPN group). Meanwhile, 42 healthy subjects were recruited as controls. The clinical characteristics (including gender, age, body mass index (BMI), and illness duration), as well as lipids (including triglyceride (TG), cholesterol (TC), low-density lipoprotein (LDL), and high-density lipoprotein (HDL)), uric acid, fasting blood glucose (FBG), and glycated hemoglobin (HbA1c) were compared among the four groups. Four groups were assessed using two vestibular tests including oVEMP and cVEMP. Latency and amplitude parameters were analyzed from VEMP plots.

Results

The latency of n10, p15 (oVEMP), p13, n23 (cVEMP) were significantly prolonged in the SDPN and DPN groups compared with the control and NDPN groups (p < 0.01), whereas latencies were similar in NDPN and the control groups. The amplitudes were not significantly different (p > 0.05). oVEMP latency p15 and cVEMP latency (p13, n23) were positively correlated with HbA1c, FBG, and illness duration, and oVEMP latency n10 was positively correlated with HbA1c and FBG. A nomogram, including FBG, HbA1C, HDL, TG, TC, LDL and group, was constructed to predict VEMP parameters and p13 was found to be independently associated with diabetic subgroups. Receiver operating characteristic curve (ROC) analysis showed good accuracy in predicting p13 in this nomogram. A user-friendly website has been created to facilitate the application of this prediction model ( https://fyey.shinyapps.io/VEMP_Model/ ).

Conclusion

Patients with diabetic peripheral neuropathy may have vestibular dysfunction. VEMP may be useful in assessing vestibular impairment in diabetic patients.