bluuebunny/crossref_metadata_2025 huggingface dataset:
Humoral immune response after Ad26.COV2.S vaccination in patients with multiple sclerosis treated with natalizumab
Authors: Gudesblatt Mark , Zarif Myassar , Bumstead Barbara , Buhse Marijean , Kaczmarek Olivia , Li Hanyue , Sun Zhaonan , Scott Nicole , Mendoza Jason P , Avila Robin L
Published: December 2023

The immunomodulatory effects of disease-modifying therapies for multiple sclerosis might affect the immune response to vaccines for severe acute respiratory syndrome coronavirus 2. We analyzed the severe acute respiratory syndrome coronavirus 2-specific antibody response and lymphocyte profile before and after Ad26.COV2.S (Johnson & Johnson) vaccination in natalizumab-treated patients with multiple sclerosis. There was a 72-fold increase in mean anti-severe acute respiratory syndrome coronavirus 2 spike immunoglobulin G levels 4 weeks after vaccination and a 137-fold increase after 6 months. Other immune signals were within normal ranges. Natalizumab-treated patients with multiple sclerosis had a robust immune response to Ad26.COV2.S vaccine, and other immune signals were not significantly affected.
Presidential Extensions in Africa 1960 to 2022: Impact on Politics, Peace, and Security
Authors: Amoah Michael
Published: December 2023

There have been 35 presidential extensions across 24 countries in Africa from 1960 to 2022, done through four categories of extension mechanisms. Most extensions occur in francophone countries, where heads-of-state govern for up to four decades and beyond, propped up by French foreign policy pacts or bilateral defense agreements which station French bases that ward of insurrections against perennial presidents. This has gestated political discontent and festered conflicts in francophone territory, to the point of being conflict-prone and terrorist enclaves. In the process, francophone Africa has attracted US drone bases for supposed counterterrorism, while Wagner mercenaries have taken up roles in countries where French Legions failed and departed. As a result, African countries have become willing or unwilling actors in the foreign policy agendas of the French, Americans, and Russians whose legions they host. Meanwhile, the African Union has the institutional frameworks to address the phenomenon of presidential extensions, but the political will is not forthcoming because the AU Assembly itself consists of several incorrigible presidents who are governing in extensions and do not want change.
Maintaining Posterior Tibial Slope and Patellar Height During Medial Opening Wedge High Tibial Osteotomy
Authors: Mabrouk Ahmed , An Jae-Sung , Fernandes Levi Reina , Kley Kristian , Jacquet Christophe , Ollivier Matthieu
Published: December 2023

Background:

Increased posterior tibial slope (PTS) and decreased patellar height (PH) after medial opening wedge high tibial osteotomy (MOWHTO) have been repeatedly reported in the literature. However, this has been disputed in more recent biomechanical studies.

Hypothesis:

No change in PTS or PH would result after MOWHTO with the freehand technique, regardless of the degree of the coronal plane correction.

Study Design:

Case series.

Methods:

A total of 62 patients who underwent MOWHTO between 2018 and 2020 were included. Surgery was performed using a dedicated step-by-step protocol to reduce the risk of unintentional slope changes. All patients were evaluated preoperatively and at a 2-year follow-up with the Knee injury and Osteoarthritis Outcome Score and the University of California, Los Angeles physical activity scale. Pre- and postoperative radiographic lower limb alignment parameters—including hip-knee-ankle angle (HKA), medial proximal tibial angle (MPTA), mechanical lateral distal femoral angle, proximal posterior tibial angle (PPTA), joint line convergence angle, and joint line obliquity—were measured on full-length lower limb radiographs. PH measurements assessed on lateral and anteroposterior knee radiographs included the Caton-Deschamps, Insall-Salvati, and Schröter indices.

Results:

A significant change was observed in the coronal plane alignment, with an increase in the MPTA from 84.38° to 90.39° ( P < .001) and a consequent increase in the HKA from 172.19° to 180.15° ( P < .001). No significant changes were observed in the PTS, as evidenced by a postoperative PPTA of 80.6° versus a preoperative value of 80.4° ( P = .2). No significant changes were detected in the mean PH on all 3 indices used—pre- versus postoperative Caton-Deschamps, Insall-Salvati, and Schröter indices measured 0.95 versus 0.93 ( P = .2), 1.03 versus 1.03 ( P = .5), and 1.56 versus 1.54 ( P = .3), respectively.

Conclusion:

In this study, MOWHTO did not result in significant changes in the PTS or PH when accurate preoperative planning and precise intraoperative freehand technique were adopted..
Rethinking the Principle of Parens Patriae: The Ariha Shah Case from a Cultural and Child Rights Perspective
Authors: Kowitz Prayathna
Published: December 2023

The aim of the work is to critically examine the encounters of an Indian child with the Jugendamt (‘Youth Office’) in Germany. The article examines the tension between protection and alienation of the child from its family and culture, questioning whether migrant, non-German children in such systems have rights, and if so what could they be? Through interviews with the family and document analysis, the study aims to establish whether the progression of the case from the position of the child has been in accordance with various United Nations human rights treaties such as the Convention on the Rights of the Child. By examining the case from a cultural, social justice and children’s rights perspective, this article concludes that unless steps are taken to dismantle the power and privilege dynamics of such institutions, children of ethnic communities will continue to be at risk of being separated from their families, in addition to being at risk of losing a variety of their rights, including the right to their cultural and religious identity.
The genetics of gaits in Icelandic horses goes beyond DMRT3, with RELN and STAU2 identified as two new candidate genes
Authors: Sigurðardóttir Heiðrún , Boije Henrik , Albertsdóttir Elsa , Kristjansson Thorvaldur , Rhodin Marie , Lindgren Gabriella , Eriksson Susanne
Published: December 2023

Background

In domesticated animals, many important traits are complex and regulated by a large number of genes, genetic interactions, and environmental influences. The ability of Icelandic horses to perform the gait ‘pace’ is largely influenced by a single mutation in the DMRT3 gene, but genetic modifiers likely exist. The aim of this study was to identify novel genetic factors that influence pacing ability and quality of the gait through a genome-wide association study (GWAS) and correlate new findings to previously identified quantitative trait loci (QTL) and mutations.

Results

Three hundred and seventy-two Icelandic horses were genotyped with the 670 K+ Axiom Equine Genotyping Array, of which 362 had gait scores from breeding field tests. A GWAS revealed several SNPs on Equus caballus chromosomes (ECA) 4, 9, and 20 that were associated (p < 1.0 × 10–5) with the breeding field test score for pace. The two novel QTL on ECA4 and 9 were located within the RELN and STAU2 genes, respectively, which have previously been associated with locomotor behavior in mice. Haplotypes were identified and the most frequent one for each of these two QTL had a large favorable effect on pace score. The second most frequent haplotype for the RELN gene was positively correlated with scores for tölt, trot, gallop, and canter. Similarly, the second most frequent haplotype for the STAU2 gene had favorable effects on scores for trot and gallop. Different genotype ratios of the haplotypes in the RELN and STAU2 genes were also observed in groups of horses with different levels of pacing ability. Furthermore, interactions (p < 0.05) were detected for the QTL in the RELN and STAU2 genes with the DMRT3 gene. The novel QTL on ECA4, 9, and 20, along with the effects of the DMRT3 variant, were estimated to account jointly for 27.4% of the phenotypic variance of the gait pace.

Conclusions

Our findings provide valuable information about the genetic architecture of pace beyond the contribution of the DMRT3 gene and indicate genetic interactions that contribute to the complexity of this trait. Further investigation is needed to fully understand the underlying genetic factors and interactions.
Dietary and lifestyle indices for hyperinsulinemia and colorectal cancer risk: a case-control study
Authors: Sicahni Pegah Hadi , Makhtoomi Maede , Leilami Kimia , Shateri Zainab , Mohammadi Farzaneh , Nouri Mehran , Omidbeigi Niloofar , Mehrabani Sanaz , Rashidkhani Bahram
Published: December 2023

Background

The incidence of colorectal cancer (CRC) has increased in Iran, and determining the dietary patterns that can contribute to reducing or increasing the risk of CRC will help better control this disease. Therefore, in the current study, we assessed the association between the empirical lifestyle index for hyperinsulinemia (ELIH) and the empirical dietary index for hyperinsulinemia (EDIH) with the CRC odds.

Methods

The present case (n = 71)-control (n = 142) study was carried out in several CRC surgical units of hospitals in Tehran, Iran. A semi-quantitative food frequency questionnaire containing 168 items was used to assess participants’ dietary intakes. The EDIH and ELIH scores were calculated by food groups and some variables such as body mass index and physical activity. Logistic regression models were applied to evaluate the association between the EDIH and ELIH scores with CRC odds.

Results

According to baseline features of the study participants, there were significant differences between the controls and cases in ELIH score, fiber intake, taking aspirin, and family history of CRC in first- and second-degree relatives. Also, we found that the odds of CRC increased significantly in the last tertile compared to the first tertile in EDIH and ELIH in the adjusted model (odds ratio (OR) = 3.12; 95% confidence interval (CI): 1.30–7.48 and OR = 4.72; 95% CI: 1.15–19.39, respectively).

Conclusions

In conclusion, the result of this study indicated that CRC odds was significantly greater in subjects with higher EDIH and ELIH scores. Also, according to the results of this study, lifestyle and diet with insulinemic potential can influence the CRC risk.
Remote at-home wearable-based gait assessments in Progressive Supranuclear Palsy compared to Parkinson’s Disease
Authors: Sharma Mansi , Mishra Ram kinker , Hall Anna J. , Casado Jose , Cole Rylee , Nunes Adonay S. , Barchard Gregory , Vaziri Ashkan , Pantelyat Alexander , Wills Anne-Marie
Published: December 2023

Background

Wearable sensors can differentiate Progressive Supranuclear Palsy (PSP) from Parkinson’s Disease (PD) in laboratory settings but have not been tested in remote settings.

Objectives

To compare gait and balance in PSP and PD remotely using wearable-based assessments.

Methods

Participants with probable PSP or probable/clinically established PD with reliable caregivers, still able to ambulate 10 feet unassisted, were recruited, enrolled, and consented remotely and instructed by video conference to operate a study-specific tablet solution (BioDigit Home ™) and to wear three inertial sensors (LEGSys™, BioSensics LLC, Newton, MA USA) while performing the Timed Up and Go, 5 × sit-to-stand, and 2-min walk tests. PSPRS and MDS-UPDRS scores were collected virtually or during routine clinical visits.

Results

Between November, 2021- November, 2022, 27 participants were screened of whom 3 were excluded because of technological difficulties. Eleven PSP and 12 PD participants enrolled, of whom 10 from each group had complete analyzable data. Demographics were well-matched (PSP mean age = 67.6 ± 1.3 years, 40% female; PD mean age = 70.3 ± 1.8 years, 40% female) while disease duration was significantly shorter in PSP (PSP 14 ± 3.5 months vs PD 87.9 ± 16.9 months). Gait parameters showed significant group differences with effect sizes ranging from d = 1.0 to 2.27. Gait speed was significantly slower in PSP: 0.45 ± 0.06 m/s vs. 0.79 ± 0.06 m/s in PD (d = 1.78, p < 0.001).

Conclusion

Our study demonstrates the feasibility of measuring gait in PSP and PD remotely using wearable sensors. The study provides insight into digital biomarkers for both neurodegenerative diseases.

Trial registration

ClinicalTrials.gov Identifier: NCT04753320, first posted Febuary 15, 2021.
Neuromuscular diseases associated with COVID-19 vaccines: a systematic review and pooled analysis of 258 patients
Authors: Tayebi Amirhossein , Samimisedeh Parham , Jafari Afshar Elmira , Mahmoudnia Saeideh , Milan Nesa , Ayati Aryan , Madady Aryan , Rastad Hadith
Published: December 2023

Background

Neuromuscular diseases (NMD) emerged as one of the main side effects of the COVID-19 vaccination. We pooled and summarized the evidence on the clinical features and outcomes of NMD associated with COVID-19 vaccination.

Methods

We comprehensively searched three databases, Medline, Embase, and Scopus, using the key terms covering “Neuromuscular disease” AND “COVID-19 vaccine”, and pooled the individual patient data extracted from the included studies.

Results

A total of 258 NMD cases following COVID-19 have been reported globally, of which 171 cases were Guillain-Barré syndrome (GBS), 40 Parsonage-Turner syndrome (PTS), 22 Myasthenia Gravis (MG), 19 facial nerve palsy (FNP), 5 single fiber neuropathy, and 1 Tolosa-Hunt syndrome. All (100%) SFN patients and 58% of FNP patients were female; in the remaining NMDs, patients were predominantly male, including MG (82%), GBS (63%), and PTS (62.5%).

The median time from vaccine to symptom was less than 2 weeks in all groups. Symptoms mainly appeared following the first dose of vector vaccine, but there was no specific pattern for mRNA-based.

Conclusion

COVID-19 vaccines might induce some NMDs, mainly in adults. The age distribution and gender characteristics of affected patients may differ based on the NMD type. About two-thirds of the cases probably occur less than 2 weeks after vaccination.
Retraction Note: Invasion inhibition in pancreatic cancer using the oral iron chelating agent deferasirox
Authors: Amano Shogo , Kaino Seiji , Shinoda Shuhei , Harima Hirofumi , Matsumoto Toshihiko , Fujisawa Koichi , Takami Taro , Yamamoto Naoki , Yamasaki Takahiro , Sakaida Isao
Published: December 2023

This article has been retracted. Please see the Retraction Notice for more detail: https://doi.org/10.1186/s12885-023-11677-6.
Pediatric cartilaginous lateral femoral condyle Hoffa fracture: a case report and review of the literature
Authors: de Beer A. , Brown M. J.
Published: December 2023

Introduction

Hoffa fractures are challenging coronally-oriented articular injuries of the femoral condyle. These fractures are rare in adults and extremely rare in the skeletally immature, with few cases reported in literature. To prevent mal- or non-union, Hoffa fractures require prompt surgical stabilisation with anatomic reduction and internal fixation.

Case report

We discuss the case of a lateral distal femoral condyle cartilaginous Hoffa fracture in a ten-year-old male patient. The patient presented after a football non-contact “twist and pop” injury with radiographic imaging described as an osteochondritis dissecans lesion. An MRI was obtained which demonstrated a lateral distal femoral condyle osteochondral fracture. An operative plan was formulated to perform arthroscopic reduction and bio-compression screw fixation to minimize damage to the physis and surrounding tissues. Hyperflexion of the knee allowed for anatomic fracture reduction with the placement of 2 bio-compression screws serving as maintenance of fixation. The patient did well postoperatively and returned to full activity after 6 months.

Conclusion

Hoffa fractures in the pediatric population are rare and can occur not only through bone but also through the thick chondral layer in younger patients. These are extremely difficult to diagnose through X-Ray alone. The prompt use of MRI imaging allows for operative fixation in a timely fashion, while an arthroscopic-only approach allows for minimal tissue damage. With an appropriate fracture type, hyper-flexion reduces and stabilizes the fracture, permitting the placement of minimally invasive bio-compression fixation.
Independent and joint trajectories of depression and anxiety symptoms among Chinese male sailors throughout a prolonged non-24-h rotating shift schedule at sea: a parallel-process growth mixture modeling approach
Authors: Tu Zhihao , Tian Fei , He Jingwen , Wang Chuan , Tian Jianquan , Shen Xinghua
Published: December 2023

Background

The predictive and protective effect of hardiness on mental health remains unclear among shift workers on non-24-h working schedules. The present study aimed to investigate the independent and joint trajectories of depression and anxiety symptoms and the role of hardiness during a prolonged period of non-24-h shift working schedule.

Methods

Four hundred nine Chinese male sailors (working on 18-h watchstanding schedule) were recruited and completed all 5-wave tests through online questionnaires (at Day 1, 14, 28, 42, 55, respectively) during a 55-day sailing. The questionnaires included sociodemographic variables, hardiness, depression and anxiety symptoms. Independent and joint trajectories of depression and anxiety symptoms were estimated by latent growth mixture models. The effect of hardiness on trajectories was examined by logistic regression models.

Results

2 and 3 latent trajectories were identified for depression and anxiety symptoms, respectively. Based on initial levels and development trends, 3 distinct joint trajectories of depression and anxiety were identifed and named as: “Low-Inverted U” group (73.6%), “Moderate-Deterioration” group (6.9%), and “High-Stable” group (9.5%). Sailors with higher levels of hardiness were more likely to follow the “Low-Inverted U” trajectory of depression and anxiety symptoms (all p < 0.001).

Conclusions

There existed individual differences in the trajectories of depression and anxiety. Hardiness may have a protective effect that can prevent and alleviate depression and anxiety symptoms. Therefore, hardiness-based intervention programs are encouraged among the shift workers on non-24-h working and rest schedules.
A systematic review on the relationship between the built environment and children’s quality of life
Authors: Kodali Hanish P. , Hitch Lisa , Dunlap Ann F , Starvaggi Marc , Wyka Katarzyna E , Huang Terry TK
Published: December 2023

Background

Evidence of the effects of the built environment on children has mainly focused on disease outcomes; however, quality of life (QoL) has gained increasing attention as an important health and policy endpoint itself. Research on built environment effects on children’s QoL could inform public health programs and urban planning and design.

Objective

We aimed to review and synthesize the evidence of the relationship between built environment features and children’s QoL.

Methods

Five research databases were searched for quantitative peer-reviewed studies on children between 2 and 18 years, published in English or German between January 2010 and August 2023. Only primary research was considered. Included studies (n = 17) were coded and methodologically assessed with the Joanna Briggs Critical Appraisal Checklists, and relevant data were extracted, analyzed, and synthesized, using the following built environment framework: (1) neighborhood green and blue space, (2) neighborhood infrastructure, and (3) neighborhood perception.

Results

Green space was positively associated with children’s QoL. Infrastructure yielded inconclusive results across all measured aspects. Overall neighborhood satisfaction was positively correlated with higher QoL but results on perceived environmental safety were mixed.

Conclusions

Most studies are correlational, making it difficult to infer causality. While the positive findings of green space on QoL are consistent, specific features of the built environment show inconsistent results. Overall perception of the built environment, such as neighborhood satisfaction, also shows more robust results compared to perceptions of specific features of the built environment. Due to the heterogeneity of both built environment and QoL measures, consistent measures of both concepts will help advance this area of research.
Learning from women veterans who navigate invisible injuries, caregiving, and reintegration challenges
Authors: Rattray Nicholas A. , Natividad Diana , Spontak Katrina , Kukla Marina , Do Ai-Nghia L. , Danson Leah , Frankel Richard M. , True Gala
Published: December 2023

Background

As women comprise a greater proportion of military service members, there is growing recognition of how their experiences in the early phase of military to civilian transitions have an important influence on their health and reintegration outcomes. Qualitative accounts of women veterans can inform programs that support transitioning service members.

Objectives

We examined narratives of civilian reintegration among women veterans to understand their experiences of adjusting to community life while coping with mental health challenges.

Methods/Participants

We interviewed 16 post-911 era women who were within 5 years of separating from military service and developed a case study based on three participants.

Main approach

Interviews were audio-recorded and transcribed verbatim. Inductive thematic analysis was conducted to establish categories about reintegration. Immersion/crystallization techniques were used to identify exemplary cases that illustrated salient themes.

Key results

Women veterans identified establishing a future career direction, drawing on social support, and navigating health care services as major factors influencing how they adjusted to civilian life. In addition, participants also highlighted the navigation of complex and intersecting identities (i.e., wife, mother, employee, friend, veteran, patient, etc.), further magnified by gender inequalities. These women performed emotional labor, which is often rendered invisible and oriented toward their family and loved ones, while simultaneously monitoring self-care activities. During the early period of reintegration, they described how they felt marginalized in terms of accessing healthcare compared to their military spouses and male veteran peers.

Conclusions

Our case study suggests that there are key gaps in addressing healthcare and readjustment needs for women servicemembers, a high priority VA group, as they transition into post-military life. It is important to consider innovative ways to address specific needs of women in veteran-focused policies and programs.
Effectiveness of mobile technology and utilization of maternal and neonatal healthcare in low and middle-income countries (LMICs): a systematic review
Authors: De Prasenjit , Pradhan Manas Ranjan
Published: December 2023

Background

Maternal and neonatal mortality are important indicators of the development of a nation and pose a severe health concern, especially in developing and Low and Middle-Income Countries (LMICs). Healthcare providers use various mobile technologies as tools to provide antenatal, delivery, and postnatal care and thereby promote maternal and child health. We conducted a systematic review to critically assess the existing literature on the effectiveness of mobile phone technology in maternal and neonatal healthcare (MNH) utilization, especially in LMICs in Asia and Africa.

Methods

A systematic search strategy was developed, and Boolean combinations of relevant keywords were utilized to search relevant literature on three electronic databases (PubMed/Medline, Scopus, and Google Scholar) from 2012 to 2022. After assessing the inclusion and exclusion criteria, 25 articles were selected for systematic review. A narrative synthesis strategy was applied to summarise the information from the included literature.

Results

This review reveals that research and evaluation studies on mobile phone or Mobile Health (mHealth) and MNH service utilization substantially varied by research designs and methodology. Most studies found that mobile phone technology is highly appreciable in improving several MNH indicators, especially in LMICs. Despite the identified benefits of mobile technology in MNH utilization, some studies also mentioned challenges related to technology use and misuse, rich-poor discrimination, and disparity in phone ownership need to be addressed.

Conclusion

There is constantly increasing evidence of mobile counseling and the use of digital technology in the MNH care system. Public health practitioners and policymakers need to make efforts to smooth the functioning of technology-based healthcare services, considering all the issues related to the confidentiality and safety of health-related data on the Internet.
Patient’s punctuality in an outpatient clinic: the role of age, medical branch and geographical factors
Authors: Cerruti Benedetta , Garavaldi Davide , Lerario Alberto
Published: December 2023

Background

The efficiency of the management of an outpatient clinic largely depends on the administration of patient flows and waiting times increase costs and affect clinical quality. In this study, we verify if the visit acceptance times are influenced by demographic or geographical factors in a large cohort of patients referred to a city and suburban private outpatient multidisciplinary clinic.

Methods

We included all scheduled visits of patients aged from 18 to 75 years who arrived in 2021, 2022 and 2023 in our private outpatient clinics, consisting of 34 medical clinics scattered in Milan metropolitan city and hinterland. The variables collected were age, visit time, check-in time, address of the medical clinic and its distance from the closest underground station, patient typology (new business vs. follow-up patient), and the medical branch of the visit. Outcome is’punctuality’, defined as check-in time minus visit time (in minutes).

Results

We considered a sample of 410.808 visits from January 2021 to April 2023. The majority of patients check-in early (84.4%) and we found that the percentage of punctual patients increases linearly with age. Earlier hours in the morning show the worst punctuality pattern as well as Blood Draws in the analysis of different medical branches. We also observed that patients who already had some activity recorded in our systems show the worst pattern of punctuality. No particular differences emerged considering the geographical location of the clinics.

Conclusions

Younger patients have worse punctuality than older patients. Moreover, earlier hour slots are the most disadvantaged and the medical specialty has an influence on the arrival habits. This data should be considered for better clinical quality and efficiency.
Stakeholder development of an implementation strategy for fall prevention in Norwegian home care – a qualitative co-creation approach
Authors: Linnerud Siv , Kvael Linda Aimee Hartford , Graverholt Birgitte , Idland Gro , Taraldsen Kristin , Brovold Therese
Published: December 2023

Background

The uptake of fall prevention evidence has been slow and limited in home care services. Involving stakeholders in the implementation process is suggested as a method to successfully tailor implementation strategies. The aim of this study was to develop an implementation strategy for fall prevention, targeting healthcare providers working in home care services.

Methods

This study used an explorative qualitative approach in a five-step co-creation process to involve researchers, service users, and healthcare providers. The first two steps consisted of workshops. This was followed by focus group interviews and individual interviews with key informants as steps three and four. Data from the first four steps were analyzed using reflexive thematic analysis. The fifth and final step was a workshop finalizing a strategy for implementing fall prevention evidence in home health services.

Results

Overall, our findings, resulted in an implementation strategy for fall prevention with four components: (1) Empower leaders to facilitate implementation, operationalized through what managers pay attention to regularly, resource priorities, and time spent on fall prevention, (2) Establish implementation teams, consisting of multidisciplinary healthcare providers from different levels of the organization, with formalized responsibility for implementation, (3) Tailor dual competence improvement, reflecting the need for knowledge and skills for fall prevention and implementation among healthcare providers and users, and (4) Provide implementation support, representing guidance through the implementation process.

Conclusions

This study advances our understanding of implementation in home care services. Implementation of fall prevention requires an implementation strategy involving a blend of essential components targeting leaders, competent healthcare providers and users, and establishing structures enhancing the implementation process.
PD-L1 blockade TAM-dependently potentiates mild photothermal therapy against triple-negative breast cancer
Authors: Wang Chao , Xu Yong-Hong , Xu Hua-Zhen , Li Ke , Zhang Quan , Shi Lin , Zhao Li , Chen Xiao
Published: December 2023

The present work was an endeavor to shed light on how mild photothermia possibly synergizes with immune checkpoint inhibition for tumor therapy. We established mild photothermal heating protocols to generate temperatures of 43 °C and 45 °C in both in vitro and in vivo mouse 4T1 triple-negative breast cancer (TNBC) models using polyglycerol-coated carbon nanohorns (CNH-PG) and 808 nm laser irradiation. Next, we found that 1) CNH-PG-mediated mild photothermia (CNH-PG-mPT) significantly increased expression of the immune checkpoint PD-L1 and type-1 macrophage (M1) markers in the TNBC tumors; 2) CNH-PG-mPT had a lower level of anti-tumor efficacy which was markedly potentiated by BMS-1, a PD-L1 blocker. These observations prompted us to explore the synergetic mechanisms of CNH-PG-mPT and BMS-1 in the context of tumor cell-macrophage interactions mediated by PD-L1 since tumor-associated macrophages (TAMs) are a major source of PD-L1 expression in tumors. In vitro, the study then identified two dimensions where BMS-1 potentiated CNH-PG-mPT. First, CNH-PG-mPT induced PD-L1 upregulation in the tumor cells and showed a low level of cytotoxicity which was potentiated by BMS-1. Second, CNH-PG-mPT skewed TAMs towards an M1-like anti-tumor phenotype with upregulated PD-L1, and BMS-1 bolstered the M1-like phenotype. The synergistic effects of BMS-1 and CNH-PG-mPT both on the tumor cells and TAMs were more pronounced when the two cell populations were in co-culture. Further in vivo study confirmed PD-L1 upregulation both in tumor cells and TAMs in the TNBC tumors following treatment of CNH-PG-mPT. Significantly, TAMs depletion largely abolished the anti-TNBC efficacy of CNH-PG-mPT alone and in synergy with BMS-1. Collectively, our findings reveal PD-L1 upregulation to be a key response of TNBC to mild photothermal stress, which plays a pro-survival role in the tumor cells while also acting as a brake on the M1-like activation of the TAMs. Blockade of mPT‑induced PD‑L1 achieves synergistic anti-TNBC efficacy by taking the intrinsic survival edge off the tumor cells on one hand and taking the brakes off the M1-like TAMs on the other. Our findings reveal a novel way (i.e. mild thermia plus PD-L1 blockade) to modulate the TAMs-tumor cell interaction to instigate a mutiny of the TAMs against their host tumor cells.

Graphical Abstract
Nomogram for predicting prolonged postoperative ileus after laparoscopic low anterior resection for rectal cancer
Authors: Guo Fangliang , Sun Zhiwei , Wang Zongheng , Gao Jianfeng , Pan Jiahao , Zhang Qianshi , Ren Shuangyi
Published: December 2023

Background

Prolonged postoperative ileus (PPOI) is a common complication after colorectal surgery that increases patient discomfort, hospital stay, and financial burden. However, predictive tools to assess the risk of PPOI in patients undergoing laparoscopic low anterior resection have not been developed. Thus, the purpose of this study was to develop a nomogram to predict PPOI after laparoscopic low anterior resection for rectal cancer.

Methods

A total of 548 consecutive patients who underwent laparoscopic low anterior resection for mid­low rectal cancer at a single tertiary medical center were retrospectively enrolled between January 2019 and January 2023. Univariate and multivariate logistic regression analysis was performed to analyze potential predictors of PPOI. The nomogram was constructed using the filtered variables and internally verified by bootstrap resampling. Model performance was evaluated by receiver operating characteristic curve and calibration curve, and the clinical usefulness was evaluated by the decision curve.

Results

Among 548 consecutive patients, 72 patients (13.1%) presented with PPOI. Multivariate logistic analysis showed that advantage age, hypoalbuminemia, high surgical difficulty, and postoperative use of opioid analgesic were independent prognostic factors for PPOI. These variables were used to construct the nomogram model to predict PPOI. Internal validation, conducted through bootstrap resampling, confirmed the great discrimination of the nomogram with an area under the curve of 0.738 (95%CI 0.736–0.741).

Conclusions

We created a novel nomogram for predicting PPOI after laparoscopic low anterior resection. This nomogram can assist surgeons in identifying patients at a heightened risk of PPOI.
The preprogrammed anti-inflammatory phenotypes of CD11chigh macrophages by Streptococcus pneumoniae aminopeptidase N safeguard from allergic asthma
Authors: Yao Shifei , Weng Danlin , Wang Yan , Zhang Yanyu , Huang Qi , Wu Kaifeng , Li Honghui , Zhang Xuemei , Yin Yibing , Xu Wenchun
Published: December 2023

Background

Early microbial exposure is associate with protective allergic asthma. We have previously demonstrated that Streptococcus pneumoniae aminopeptidase N (PepN), one of the pneumococcal components, inhibits ovalbumin (OVA) -induced airway inflammation in murine models of allergic asthma, but the underlying mechanism was incompletely determined.

Methods

BALB/c mice were pretreated with the PepN protein and exposed intranasally to HDM allergen. The anti-inflammatory mechanisms were investigated using depletion and adoptive transfer experiments as well as transcriptome analysis and isolated lung CD11chigh macrophages.

Results

We found pretreatment of mice with PepN promoted the proliferation of lung-resident F4/80+CD11chigh macrophages in situ but also mobilized bone marrow monocytes to infiltrate lung tissue that were then transformed into CD11high macrophages. PepN pre-programmed the macrophages during maturation to an anti-inflammatory phenotype by shaping the metabolic preference for oxidative phosphorylation (OXPHOS) and also inhibited the inflammatory response of macrophages by activating AMP-activated protein kinase. Furthermore, PepN treated macrophages also exhibited high-level costimulatory signaling molecules which directed the differentiation into Treg.

Conclusion

Our results demonstrated that the expansion of CD11chigh macrophages in lungs and the OXPHOS metabolic bias of macrophages are associated with reduced allergic airway inflammation after PepN exposure, which paves the way for its application in preventing allergic asthma.
The potential role of omentin-1 in obesity-related metabolic dysfunction-associated steatotic liver disease: evidence from translational studies
Authors: Salvoza Noel , Giraudi Pablo , Gazzin Silvia , Bonazza Deborah , Palmisano Silvia , de Manzini Nicolò , Zanconati Fabrizio , Raseni Alan , Sirianni Francesca , Tiribelli Claudio , Rosso Natalia
Published: December 2023

Background

Obesity, characterized by visceral adipose tissue (VAT) expansion, is closely associated with metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH). Recent research has highlighted the crucial role of the adipose tissue—liver axis in the development of MASLD. In this study, we investigated the potential role of omentin-1, a novel adipokine expressed by VAT, in obesity-related MASLD pathogenesis.

Methods

Through in silico analysis of differentially expressed genes in VAT from obese patients with and without MASH, we identified omentin-1 as a significant candidate. To validate our findings, we measured omentin-1 levels in VAT and plasma of lean controls and obese patients with biopsy-proven MASLD. Additionally, we assessed omentin-1 expression in the VAT of diet-induced mice MASLD model. In vitro and ex vivo studies were conducted to investigate the effects of omentin-1 on MASLD-related mechanisms, including steatosis, inflammation, endoplasmic reticulum (ER) stress, and oxidative stress. We also analyzed the impact ofd-glucose and insulin on VAT omentin-1 levels ex vivo.

Results

Compared to the lean group, the obese groups exhibited significantly lower VAT and plasma levels of omentin-1. Interestingly, within the obese groups, omentin-1 is further decreased in MASH groups, independent of fibrosis. Likewise, VAT of mice fed with high-fat diet, showing histological signs of MASH showed decreased omentin-1 levels as compared to their control diet counterpart. In vitro experiments on fat-laden human hepatocytes revealed that omentin-1 did not affect steatosis but significantly reduced TNF-α levels, ER stress, and oxidative stress. Similar results were obtained using ex vivo VAT explants from obese patients upon omentin-1 supplementation. Furthermore, omentin-1 decreased the mRNA expression ofNF-κBand mitogen-activated protein kinases (ERKandJNK). Ex vivo VAT explants showed thatd-glucose and insulin significantly reduced omentin-1 mRNA expression and protein levels.

Conclusions

Collectively, our findings suggest that reduced omentin-1 levels contribute to the development of MASLD. Omentin-1 supplementation likely exerts its beneficial effects through the inhibition of the NF-κB and MAPK signaling pathways, and it may additionally play a role in the regulation of glucose and insulin metabolism. Further research is warranted to explore omentin-1 as a potential therapeutic target and/or biomarker for MASLD.

Graphical Abstract
The expanding Pandora’s toolbox of CD8+T cell: from transcriptional control to metabolic firing
Authors: Wu Jinghong , Lu Zhendong , Zhao Hong , Lu Mingjun , Gao Qing , Che Nanying , Wang Jinghui , Ma Teng
Published: December 2023

CD8+ T cells are the executor in adaptive immune response, especially in anti-tumor immunity. They are the subset immune cells that are of high plasticity and multifunction. Their development, differentiation, activation and metabolism are delicately regulated by multiple factors. Stimuli from the internal and external environment could remodel CD8+ T cells, and correspondingly they will also make adjustments to the microenvironmental changes. Here we describe the most updated progresses in CD8+ T biology from transcriptional regulation to metabolism mechanisms, and also their interactions with the microenvironment, especially in cancer and immunotherapy. The expanding landscape of CD8+ T cell biology and discovery of potential targets to regulate CD8+ T cells will provide new viewpoints for clinical immunotherapy.
Vesicular HMGB1 release from neurons stressed with spreading depolarization enables confined inflammatory signaling to astrocytes
Authors: Kaya Zeynep , Belder Nevin , Sever-Bahcekapili Melike , Donmez-Demir Buket , Erdener Şefik Evren , Bozbeyoglu Naz , Bagci Canan , Eren-Kocak Emine , Yemisci Muge , Karatas Hulya , Erdemli Esra , Gursel Ihsan , Dalkara Turgay
Published: December 2023

The role of high mobility group box 1 (HMGB1) in inflammation is well characterized in the immune system and in response to tissue injury. More recently, HMGB1 was also shown to initiate an “inflammatory signaling cascade” in the brain parenchyma after a mild and brief disturbance, such as cortical spreading depolarization (CSD), leading to headache. Despite substantial evidence implying a role for inflammatory signaling in prevalent neuropsychiatric disorders such as migraine and depression, how HMGB1 is released from healthy neurons and how inflammatory signaling is initiated in the absence of apparent cell injury are not well characterized. We triggered a single cortical spreading depolarization by optogenetic stimulation or pinprick in naïve Swiss albino or transgenic Thy1-ChR2-YFP and hGFAP-GFP adult mice. We evaluated HMGB1 release in brain tissue sections prepared from these mice by immunofluorescent labeling and immunoelectron microscopy. EzColocalization and Costes thresholding algorithms were used to assess the colocalization of small extracellular vesicles (sEVs) carrying HMGB1 with astrocyte or microglia processes. sEVs were also isolated from the brain after CSD, and neuron-derived sEVs were captured by CD171 (L1CAM). sEVs were characterized with flow cytometry, scanning electron microscopy, nanoparticle tracking analysis, and Western blotting. We found that HMGB1 is released mainly within sEVs from the soma of stressed neurons, which are taken up by surrounding astrocyte processes. This creates conditions for selective communication between neurons and astrocytes bypassing microglia, as evidenced by activation of the proinflammatory transcription factor NF-ĸB p65 in astrocytes but not in microglia. Transmission immunoelectron microscopy data illustrated that HMGB1 was incorporated into sEVs through endosomal mechanisms. In conclusion, proinflammatory mediators released within sEVs can induce cell-specific inflammatory signaling in the brain without activating transmembrane receptors on other cells and causing overt inflammation.
Maternal exposure to nano-titanium dioxide impedes fetal development via endothelial-to-mesenchymal transition in the placental labyrinth in mice
Authors: Li Xianjie , Luo Yinger , Ji Di , Zhang Zhuyi , Luo Shili , Ma Ya , Cao Wulan , Cao Chunwei , Saw Phei Er , Chen Hui , Wei Yanhong
Published: December 2023

Background

Extensive production and usage of commercially available products containing TiO2 NPs have led to accumulation in the human body. The deposition of TiO2 NPs has even been detected in the human placenta, which raises concerns regarding fetal health. Previous studies regarding developmental toxicity have frequently focused on TiO2 NPs < 50 nm, whereas the potential adverse effects of large-sized TiO2 NPs received less attention. Placental vasculature is essential for maternal–fetal circulatory exchange and ensuring fetal growth. This study explores the impacts of TiO2 NPs (100 nm in size) on the placenta and fetal development and elucidates the underlying mechanism from the perspective of placental vasculature. Pregnant C57BL/6 mice were exposed to TiO2 NPs by gavage at daily dosages of 10, 50, and 250 mg/kg from gestational day 0.5–16.5.

Results

TiO2 NPs penetrated the placenta and accumulated in the fetal mice. The fetuses in the TiO2 NP-exposed groups exhibited a dose-dependent decrease in body weight and length, as well as in placental weight and diameter. In vivo imaging showed an impaired placental barrier, and pathological examinations revealed a disrupted vascular network of the labyrinth upon TiO2 NP exposure. We also found an increase in gene expression related to the transforming growth factor-β (TGF-β) -SNAIL pathway and the upregulation of mesenchymal markers, accompanied by a reduction in endothelial markers. In addition, TiO2 NPs enhanced the gene expression responsible for the endothelial-to-mesenchymal transition (EndMT) in cultured human umbilical vein endothelial cells, whereas SNAIL knockdown attenuated the induction of EndMT phenotypes.

Conclusion

Our study revealed that maternal exposure to 100 nm TiO2 NPs disrupts placental vascular development and fetal mice growth through aberrant activation of EndMT in the placental labyrinth. These data provide novel insight into the mechanisms of developmental toxicity posed by NPs.
Audit and feedback to reduce unwarranted clinical variation at scale: a realist study of implementation strategy mechanisms
Authors: Sarkies Mitchell , Francis-Auton Emilie , Long Janet , Roberts Natalie , Westbrook Johanna , Levesque Jean-Frederic , Watson Diane E. , Hardwick Rebecca , Sutherland Kim , Disher Gary , Hibbert Peter , Braithwaite Jeffrey
Published: December 2023

Background

Unwarranted clinical variation in hospital care includes the underuse, overuse, or misuse of services. Audit and feedback is a common strategy to reduce unwarranted variation, but its effectiveness varies widely across contexts. We aimed to identify implementation strategies, mechanisms, and contextual circumstances contributing to the impact of audit and feedback on unwarranted clinical variation.

Methods

Realist study examining a state-wide value-based healthcare program implemented between 2017 and 2021 in New South Wales, Australia. Three initiatives within the program included audit and feedback to reduce unwarranted variation in inpatient care for different conditions. Multiple data sources were used to formulate the initial audit and feedback program theory: a systematic review, realist review, program document review, and informal discussions with key program stakeholders. Semi-structured interviews were then conducted with 56 participants to refute, refine, or confirm the initial program theories. Data were analysed retroductively using a context-mechanism-outcome framework for 11 transcripts which were coded into the audit and feedback program theory. The program theory was validated with three expert panels: senior health leaders (n = 19), Agency for Clinical Innovation (n = 11), and Ministry of Health (n = 21) staff.

Results

The program’s audit and feedback implementation strategy operated through eight mechanistic processes. The strategy worked well when clinicians (1) felt ownership and buy-in, (2) could make sense of the information provided, (3) were motivated by social influence, and (4) accepted responsibility and accountability for proposed changes. The success of the strategy was constrained when the audit process led to (5) rationalising current practice instead of creating a learning opportunity, (6) perceptions of unfairness and concerns about data integrity, 7) development of improvement plans that were not followed, and (8) perceived intrusions on professional autonomy.

Conclusions

Audit and feedback strategies may help reduce unwarranted clinical variation in care where there is engagement between auditors and local clinicians, meaningful audit indicators, clear improvement plans, and respect for clinical expertise. We contribute theoretical development for audit and feedback by proposing a Model for Audit and Feedback Implementation at Scale. Recommendations include limiting the number of audit indicators, involving clinical staff and local leaders in feedback, and providing opportunities for reflection.