bluuebunny/crossref_metadata_2025 huggingface dataset:
Surgical Management of Pediatric Dermatofibrosarcoma Protuberans: About Two Challenging Case Reports
Authors: Zouirech Yacine , Manni Abir , Rouijel Badr , El Baoudi Ahmed , El Agouri Hajar , Fejjal Nawfal
Published: September 2024

Dermatofibrosarcoma protuberans (DFSP) is an extremely rare cutaneous tumor in children, marked by local aggressiveness, slow growth, high recurrence rate, and low metastatic potential. Its prevalence is often underestimated in children due to its slow growth and frequent misdiagnosis. Diagnosing DFSP can be challenging due to nonspecific symptoms. While most cases present as nodular lesions on the trunk or proximal extremities, some lesions, such as atrophic plaques or sclerotic nodular plaques, can mimic vascular malformations and confuse clinicians. Histologic and immunohistochemical studies are essential for definitive diagnosis. The treatment of choice is complete surgical resection with wide margins to reduce the risk of recurrence. We report two pediatric DFSP cases on the trunk, including one mimicking vascular malformations. Both cases had successful 4 cm margin resections, with no recurrences observed after 6 months and 2 years of follow-up, respectively. Continuous surveillance will be maintained for at least 5 years.
Historical Patterns and Trends in Racial/Ethnic Disproportionality in School Discipline in the United States
Authors: Gopalan Maithreyi , Asson Sarah , Cattell Michael , Frankenberg Erica
Published: September 2024

This visualization represents the historical patterns and trends in racial/ethnic differences in punitive school discipline over the last five decades in K–12 public schools in the United States. Overall, out-of-school suspension rates show an inverted-U trend with significant increases between 1970 and 2010 followed by decreases in the last decade. On the other hand, corporal punishment rates (and associated racial/ethnic disparities) show a consistent negative trend since the early 1980s following statewide bans in the use of corporal punishment in schools since the 1970s. However, racial/ethnic disproportionality in school discipline remains persistent across the board; indeed, increasing until the very last few years for Black and American Indian/Alaskan Native students compared to White students.
Mentoring for Admission and Retention of Black Socio-Ethnic Minorities in Medicine: A Scoping Review
Authors: Kemzang Julia , Bekolo Gaelle , Jaunky Sarvesh , Mathieu Johanne , Constant Hérold , Oguntala Julianah , Rahmani Malek , Louismé Michael Christopher , Medina Natalia , Kendall Claire E. , Ewurabena Simpson , Hubert Daniel , Domecq Marie-Cécile , Fotsing Salomon
Published: September 2024

Purpose

Despite numerous mentoring strategies to promote academic success and eligibility in medicine, Black students remain disproportionately underrepresented in medicine. Therefore, we conducted a scoping review to identify the mentoring practices available to Black pre-medical students, medical students and medical residents, specifically the mentoring strategies used, their application, and their evaluation.

Method

Between May 2023 and October 2023, the authors conducted a literature review. Studies that described a mentoring strategy applied among Black learners were eligible for inclusion, and all years of publication were included. Two reviewers screened each article using the Covidence tool, and conflicts were resolved by a third author. All reviewers extracted the data to summarize the various mentoring practices.

Results

After screening 6292 articles, 42 articles met the criteria for full review. Of these, 14 studies were included in the study. Mentoring practices for Black students included peer mentoring, dyad mentoring, and group mentoring. Mentoring was typically offered through discussion groups, educational internships, and didactic activities. Evaluation of mentoring programs took into account (1) pass rates on medical exams (eg, MCAT, Casper), (2) receipt of an invitation to a medical school admissions interview, (3) successful match to a competitive residency program, and (4) a mentee's report of the overall experience and effectiveness of the program.

Conclusion

This review is the first, to our knowledge, to focus on mentoring strategies implemented among Black learners in medicine. The results will inform mentoring strategies adapted for Black learners and will therefore address the underrepresentation of Black students in medicine.
The future of underground mine planning in the era of machine learning: Opportunities for engineering robustness and flexibility
Authors: Chimunhu Prosper , Topal Erkan , Asad Mohammad Waqar Ali , Faradonbeh Roohollah Shirani , Ajak Ajak Duany
Published: September 2024

Machine learning (ML) applications are increasing their footprint in underground mine planning, enabled by the gradual enrichment of research methods. Indeed, improvements in prediction results have been accelerated in areas such as mining dilution, stope stability, ore grade, and equipment availability, among others. In addition, the increasing deployment of equipment with digital technologies and rapid information retrieval sensor networks is resulting in the production of immense quantities of operational data. However, despite these favourable developments, optimisation studies on key input activities are still siloed, with minimal or no synergies towards the primary objective of optimising the production schedule. As such, the full potential of ML benefits is not realised. To explore the potential benefits, this study outlines primary input areas in production scheduling for reference and limits the scope to six key areas, covering dilution prediction, ore grade variability, geotechnical stability, ventilation, mineral commodity prices and data management. The study then delves into the literature of each before examining the limitations of existing common applications, including ML. Finally, conclusions with recommendations/solutions to enhance resilience, global optimality, and reliability of the production schedule through synergistic nexus with function-specific optimised input models are presented.
Stage III NSCLC treatment options: too many choices
Authors: Asmara Oke Dimas , Hardavella Georgia , Ramella Sara , Petersen René Horsleben , Tietzova Ilona , Boerma E. Christiaan , Tenda Eric Daniel , Bouterfas Asmaa , Heuvelmans Marjolein A. , van Geffen Wouter H.
Published: October 2024

Stage III nonsmall cell lung cancer (NSCLC) represents a wide range of tumour (T1 to T4) and nodal (N0 to N3) components, requiring variable management and a multidisciplinary approach. Recent advancements in minimally invasive techniques, molecular biology and novel drug discoveries have accelerated the refinement of stage III NSCLC management. The latest developments in staging include the forthcoming update of the nodal component in the 9th TNM (tumour–node–metastasis) edition, which emphasises the critical role for endobronchial ultrasonography in mediastinal staging. Recent treatment developments include the use of immunotherapy and targeted molecular therapy in both the neoadjuvant and adjuvant setting, either in combination with other modalities or used alone as consolidation. Surgical and radiotherapy advancements have further enhanced patient outcomes. These developments have significantly improved the prognosis for patients with stage III NSCLC. Fast-changing recommendations have also brought about a challenge, with clinicians facing a number of options to choose from. Therefore, a multimodal approach by a multidisciplinary team has become even more crucial in managing stage III NSCLC.
SOST/Sclerostin impairs the osteogenesis and angiogesis in glucocorticoid-associated osteonecrosis of femoral head
Authors: Huang Junming , Ma Tianle , Wang Chenzhong , Wang Zhe , Wang Xinyuan , Hua Bingxuan , Jiang Chang , Yan Zuoqin
Published: September 2024

Background

Glucocorticoid-associated osteonecrosis of the femoral head (GA-ONFH) is a progressive bone disorder which frequently results in femoral head collapse and hip joint dysfunction. Sclerostin (SOST) is principally secreted by osteocytes in bone and plays an important role in bone homeostasis and homeostasis of skeletal integrity. Our previous study reported that short‐term use of glucocorticoid increased serum sclerostin levels. Here this study is aimed to identify whether sclerostin played an essential role in the occurrence and development of GA-ONFH.

Methods

Glucocorticoid-induced osteonecrosis of femoral head (ARCO stage II) samples were collected and sclerostin staining was conducted. Osteocyte cell line Ocy454, MC3T3-E1 and endothelial cells was used. MC3T3-E1 or endothelial cells were co-cultured with Ocy454 or SOST-silencing Ocy454 in presence of dexamethasone to mimic the crosstalk of various cells in the bone niche. GA-ONFH rat model and SOST knockout model was built to better understand the phenomenon in vivo.

Results

Sclerostin was highly concentrated in osteonecrosis patient sample in the necrotic area. Co-culture with osteocytes aggravated the inhibition of dexamethasone on MC3T3-E1 and endothelial cells. Sclerostin derived from osteocytes impaired osteogenesis and angiogenesis via inhibiting the Wnt pathway. In GA-ONFH rat model, SOST knockout ameliorated the incidence of osteonecrosis and improved bone metabolism compared with the wild type group through histological, immunohistochemical and bone metabolic analyses.

Conclusion

Sclerostin contribute to pathologic process of GA-ONFH by impairing osteogenesis and angiogenesis.
Symbiotic bacteria Sodalis glossinidius, Spiroplasma sp and Wolbachia do not favour Trypanosoma grayi coexistence in wild population of tsetse flies collected in Bobo-Dioulasso, Burkina Faso
Authors: Mfopit Youssouf Mouliom , Bilgo Etienne , Boma Soudah , Somda Martin Bienvenu , Gnambani Jacques Edounou , Konkobo Maurice , Diabate Abdoulaye , Dayo Guiguigbaza-Kossigan , Mamman Mohammed , Kelm Soerge , Balogun Emmanuel Oluwadare , Shuaibu Mohammed Nasir , Kabir Junaidu
Published: September 2024

Background

Tsetse flies, the biological vectors of African trypanosomes, have established symbiotic associations with different bacteria. Their vector competence is suggested to be affected by bacterial endosymbionts. The current study provided the prevalence of three tsetse symbiotic bacteria and trypanosomes in Glossina species from Burkina Faso.

Results

A total of 430 tsetse flies were captured using biconical traps in four different collection sites around Bobo-Dioulasso (Bama, Bana, Nasso, and Peni), and their guts were removed. Two hundred tsetse were randomly selected and their guts were screened by PCR for the presence of Sodalis glossinidius, Spiroplasma sp., Wolbachia and trypanosomes. Of the 200 tsetse, 196 (98.0%) were Glossina palpalis gambiensis and 4 (2.0%) Glossina tachinoides. The overall symbiont prevalence was 49.0%, 96.5%, and 45.0%, respectively for S. glossinidius, Spiroplasma and Wolbachia. Prevalence varied between sampling locations: S. glossinidius (54.7%, 38.5%, 31.6%, 70.8%); Spiroplasma (100%, 100%, 87.7%, 100%); and Wolbachia (43.4%, 38.5%, 38.6%, 70.8%), respectively in Bama, Bana, Nasso and Peni. Noteworthy, no G. tachnoides was infected by S. glossinidius and Wolbachia, but they were all infected by Spiroplasma sp. A total of 196 (98.0%) harbored at least one endosymbionts. Fifty-five (27.5%) carried single endosymbiont. Trypanosomes were found only in G. p. gambiensis, but not G. tachinoides. Trypanosomes were present in flies from all study locations with an overall prevalence of 29.5%. In Bama, Bana, Nasso, and Peni, the trypanosome infection rate was respectively 39.6%, 23.1%, 8.8%, and 37.5%. Remarkably, only Trypanosoma grayi was present. Of all trypanosome-infected flies, 55.9%, 98.3%, and 33.9% hosted S. glossinidius, Spiroplasma sp and Wolbachia, respectively. There was no association between Sodalis, Spiroplasma and trypanosome presence, but there was a negative association with Wolbachia presence. We reported 1.9 times likelihood of trypanosome absence when Wolbachia was present.

Conclusion

This is the first survey reporting the presence of Trypanosoma grayi in tsetse from Burkina Faso. Tsetse from these localities were highly positive for symbiotic bacteria, more predominantly with Spiroplasma sp. Modifications of symbiotic interactions may pave way for disease control.
“Like an umbrella, protecting me from the rain until I get to my destination”: Evaluating the implementation of a tailored primary care model for urban marginalized populations
Authors: Khorsand Soha , Geller Carol , Eyre Alison , Abi Haidar Hounaida , Chen Haifeng , Lacombe Corina , Kabir Monisha , Mclellan Andrew
Published: September 2024

Background

Improving health equity and access to the highest possible standard of health care is a key issue of social accountability. Centretown Community Health Centre in Ottawa, Canada has iteratively developed a program to target and serve marginalized and complex populations since 1999. The program implementation was evaluated using a validated implementation framework.

Methods

Quantitative and qualitative data were collected through a health records extraction (n = 570), a client complexity assessment tool (n = 74), semi-structured interviews with clients and key stakeholders (n = 41), and a structured client satisfaction survey (n = 30). Data were analyzed using descriptive statistics and inductive thematic analysis.

Results

Five hundred and seventy unique clients were seen between November 1–30, 2021. A third of clients (34%) did not have a provincial health card for access to universal health care services, and most (68%) were homeless or a resident of rooming houses. Most clients who reported their income (92%) were at or below Canada’s official poverty line.

The total mean complexity score for clients seen over a one-month period (n = 74) was 16.68 (SD 6.75) where a total score of at least 13 of 33 is perceived to be a threshold for client biopsychosocial complexity. Clients gained the majority of their total score from the Social support assessment component of the tool.

Clients (n = 31) and key informants (n = 10) highlighted the importance of building relationships with this population, providing wrap-around care, and providing low-barrier care as major strength to the Urban Health program (UH). Key areas for improvement included the need to: i) increase staff diversity, ii) expand program hours and availability, and iii) improve access to harm reduction services. Clients appeared to be highly satisfied with the program, rating the program an average total score of 18.50 out of 20.

Conclusions

The program appears to serve marginalized and complex clients and seems well-received by the community. Our findings have relevance for other health care organizations seeking to better serve marginalized and medically and socially complex individuals and families in their communities.
A method of “Noninjecting Resection using Bipolar Soft coagulation mode; NIRBS” for superficial non-ampullary duodenal epithelial tumor: a pilot study
Authors: Tokuhara Mitsuo , Sano Yasushi , Watanabe Yoshifumi , Nakata Hidetoshi , Nakahira Hiroko , Furukawa Shingo , Ohtsu Takuya , Nakamura Naohiro , Ito Takashi , Torii Ikuko , Yamashina Takeshi , Shimatani Masaaki , Naganuma Makoto
Published: October 2024

Background

Complete endoscopic resection of superficial non-ampullary duodenal epithelial tumors (SNADETs) is technically difficult, especially with an extremely high risk of adverse event (AE), although various endoscopic resection methods including endoscopic mucosal resection (EMR), underwater EMR (UEMR), and endoscopic submucosal dissection (ESD) have been tried for SNADETs. Accordingly, a novel simple resection method that can completely resect tumors with a low risk of AEs should be developed.

Aims

A resection method of Noninjecting Resection using Bipolar Soft coagulation mode (NIRBS) which has been reported to be effective and safe for colorectal lesions is adapted for SNADETs. In this study we evaluated its effectiveness, safety, and simplicity for SNADETs measuring ≤ 20 mm.

Results

This study included 13 patients with resected lesions with a mean size of 7.8 (range: 3–15) mm. The pathological distributions of the lesions were as follows: adenomas, 77% (n = 10) and benign and non-adenomatous lesions, 23% (n = 3). The en bloc and R0 resection rate was 100% (n = 13). The median procedure duration was 68 s (32–105). None of the patients presented with major AEs including bleeding and perforation.

Conclusions

Large studies such as prospective, randomized, and controlled trials should be conducted for the purpose of validating effectiveness, safety, and simplicity of the NIRBS for SNADETs measuring ≤ 20 mm suggested in this study.
Developing a research agenda on NATure-based and Animal-assisted Intervention Strategies (NATAIS) in people with neurodegenerative diseases with a specific focus on social isolation and loneliness: a group concept mapping procedure
Authors: Declercq I. J. N. , Leontjevas R. , Enders-Slegers M.-J. , Molog M. , Gerritsen D. L. , Hediger K. ,   on behalf of NATAIS Working Group, Bos Sieka , de Bruin Simone , Halck Birgitta Erixon , Hoorelbeke Sofie , Janssens Mayke , van der Leest Yvonne , van Meel Dorit , Ng Zenithson , Olsen Christine , Ormerod Elizabeth , Pedersen Ingeborg , Reniers Peter , Wesenberg Sandra , Ellis Jules , Eshuis Jannes , Gee Nancy , Griffioen Richard , Groenewoud Danielle , Haven-Pross Sandra , Janus Sarah , Mills Daniel , Ojo Victor , Pendry Patricia , Rosteius Katharina , de Vugt Marjolein , Zuidema Sytse
Published: September 2024

Background

Social isolation and feelings of loneliness are very prevalent in people with neurodegenerative diseases and are associated with a lower quality of life and other negative outcomes. These problems were increased during the COVID-19 pandemic resulting in initiatives to address social isolation. Given the potential benefits of nature-based and animal-assisted intervention strategies (NATAIS), it is crucial to further investigate if and how these strategies might minimize negative effects of social isolation and feelings of loneliness in this population. Therefore, the aim of this project was to develop a research agenda for NATAIS in people with neurodegenerative diseases, especially during challenging times, such as pandemics.

Methods

This article outlines the process and results of a group concept mapping procedure aimed at developing a research agenda based on a logic model. In total, 19 work group members participated through a combination of in-person and online group meetings. Additionally, face-to-face group sessions were held at two international scientific conferences, during which feedback was solicited from 12 experts in the field of NATAIS and psychogeriatrics.

Results

The group concept mapping procedure resulted in 14 clusters describing various future research topics, which were further refined and detailed during group discussions. The remaining eleven clusters, encompassing important research themes within the field of NATAIS, were organized into a logic model and summarized into the research agenda. The overarching cluster ‘ethical issues, possible risk factors, and their solutions’ was considered the most relevant during times of increased social isolation, such as during a pandemic, along with the necessity for more accessible NATAIS.

Conclusions

This project resulted in a research agenda, directing future research and fostering collaboration between practitioners and researchers in the field of NATAIS. Such an enhanced partnership between science and practice has the potential to significantly contribute to the well-being of people with neurodegenerative diseases, in their daily lives and also during pandemics.
Criterion validity of a single-item measure of fear avoidance behavior following mild traumatic brain injury
Authors: Amin Shahrazad , Mikolic Ana , Silverberg Noah D.
Published: September 2024

Maladaptive coping such as fear avoidance behavior can prolong recovery from mild traumatic brain injury (mTBI). Routine assessment of fear avoidance may improve management of mTBI. This study aimed to validate a single-item measure of fear avoidance to make its assessment more pragmatic. The present study is a secondary analysis of a clinical trial that involved adults with persistent post-concussion symptoms (N = 90, 63% female). Participants completed the single-item fear avoidance rating, a validated legacy measure of fear avoidance (Fear Avoidance Behavior after Traumatic Brain Injury; FAB-TBI), and measures of anxiety (General Anxiety Disorder-7), depression (Patient Health Questionnaire-9), post-concussion symptoms (Rivermead Postconcussion Symptoms Questionnaire), and disability (World Health Organization Disability Assessment Schedule 12.0). Questionnaires were completed twice, at baseline (mean 18.1 weeks post injury) and again 12–16 weeks later following study-delivered rehabilitation in addition to usual care. We analyzed the associations (Spearman’s correlations) and agreement (weighted Kappa) between the single-item and FAB-TBI at baseline, posttreatment, individual FAB-TBI item scores, and the change in scores between baseline and posttreatment. In addition, we examined correlations between the single-item fear avoidance measure and related constructs, including anxiety, depression, post-concussion symptoms, and disability. The single-item fear avoidance measure correlated strongly with the FAB-TBI both at baseline and following treatment (ρ = 0.63 − 0.67, p < .001), and moderately with FAB-TBI item scores (ρ = 0.4 − 0.6). The correlation between the change in these scores from baseline to posttreatment was moderate (ρ = 0.45, p < .001). Agreement between the single-item fear avoidance measure and discretized FAB-TBI scores was moderate (κ = 0.45 − 0.51). Before and after treatment, the single-item fear avoidance measure correlated moderately with anxiety (ρ = 0.34), depression (ρ = 0.43), post-concussion symptoms (ρ = 0.50), and disability (ρ = 0.43). The FAB-TBI was more strongly correlated with these measures (ρ = 0.53 − 0.73). In summary, the present study supports the criterion validity of the single-item fear avoidance measure. This measure may be a useful screening and monitoring tool for patients with mTBI but is not a substitute for the FAB-TBI questionnaire.
Woodhouse-sakati syndrome with no reportable MRI findings: a case report
Authors: Irvine Rebecca Eilish , Ahmad Arshia
Published: September 2024

Background

Woodhouse-Sakati Syndrome (WSS) is a rare autosomal recessive condition caused by biallelic pathogenic variants in the DCAF17 gene, with fewer than 200 cases reported in the literature. Symptoms first emerge in middle-late adolescence with a spectrum of hypogonadal and progressive neurological features.

Case presentation

We present a case of WSS with no reportable T2-weighted, apparent diffusion coefficient mapping and susceptibility weighted MRI findings. This differs from cases reported in the current literature. Our patient developed abnormal movements in both legs, clumsiness of the hands, dysarthria, and swallowing difficulties. Moreover, she presented with alopecia manifesting as frontal and temporal balding, severe dystonia with painful dystonic spasms primarily in the left upper limb, as well as primary amenorrhea. She was not independently ambulatory on presentation, requiring wheelchair assistance. Genetic testing, the crucial test for a definitive diagnosis, was undertaken in Qatar and confirmed WSS. Treatment provided includes botulinum toxin injections and deep brain stimulation, providing better dystonia control, with progress in walking and strength exercises, and overall remarkable improvement. Intensive neurorehabilitation regimes were also deployed from admission, including physiotherapy, occupational therapy and speech and language therapy.

Conclusion

This case adds to the current literature on WSS manifestations, with all previously reported cases having positive MRI findings, unlike our case.
Mindfulness to enhance quality of life and support advance care planning: a pilot randomized controlled trial for adults with advanced cancer and their family caregivers
Authors: Mosher Catherine E. , Beck-Coon Kathleen A. , Wu Wei , Lewson Ashley B. , Stutz Patrick V. , Brown Linda F. , Tang Qing , Helft Paul R. , Levoy Kristin , Hickman Susan E. , Johns Shelley A.
Published: September 2024

Background

Patients with advanced cancer and family caregivers often use avoidant coping strategies, such as delaying advance care planning discussions, which contribute to deterioration in their quality of life. Mindfulness-based interventions have shown promise in improving quality of life in this population but have rarely been applied to advance care planning. This pilot trial examined the preliminary efficacy of a group-based Mindfulness to Enhance Quality of Life and Support Advance Care Planning (MEANING) intervention for patient-caregiver dyads coping with advanced cancer. Primary outcomes were patient and caregiver quality of life or well-being, and secondary outcomes included patient advanced care planning engagement (self-efficacy and readiness) and other psychological and symptom outcomes.

Methods

In this pilot trial, dyads coping with advanced cancer were recruited from five oncology clinics in the midwestern U.S. and randomized to six weekly group sessions of a mindfulness intervention (n = 33 dyads) or usual care (n = 22 dyads). Outcomes were assessed via surveys at baseline, post-intervention, and 1 month post-intervention. All available data were included in the multilevel models assessing intervention efficacy.

Results

Patients in the MEANING condition experienced significant increases in existential well-being and self-efficacy for advance care planning across follow-ups, whereas usual care patients did not. Other group differences in outcomes were not statistically significant. These outcomes included other facets of patient well-being, caregiver quality of life, patient readiness for advance care planning, caregiver burden, and patient and caregiver depressive symptoms, anxiety, sleep disturbance, cognitive avoidance, and peaceful acceptance of cancer. However, only MEANING patients showed moderate increases in psychological well-being across follow-ups, and MEANING caregivers showed moderate increases in quality of life at 1-month follow-up. Certain psychological outcomes, such as caregiver burden at 1-month follow-up, also showed moderate improvement in the MEANING condition. Patients in both conditions reported small to moderate increases in readiness to engage in advance care planning.

Conclusions

A mindfulness-based intervention showed promise in improving quality-of-life and advance care planning outcomes in patients and caregivers coping with advanced cancer and warrants further testing.

Trial Registration

ClinicalTrials.gov NCT03257007. Registered 22 August 2017, https://clinicaltrials.gov/ct2/show/NCT03257007.
Piperine, a black pepper compound, induces autophagy and cellular senescence mediated by NF-κB and IL-6 in acute leukemia
Authors: Charoensedtasin Kantorn , Kheansaard Wasinee , Roytrakul Sittiruk , Tanyong Dalina
Published: September 2024

Acute leukemia is characterized by abnormal white blood cell proliferation with rapid onset and severe complications. Natural compounds, which are alternative treatments, are widely used in cancer treatment. Piperine, an alkaloid compound from black pepper, exerts anticancer effects through the cell death signaling pathway. Autophagy and senescence signaling pathways are considered target signaling pathways for cancer treatment. In this study, we investigated the effects of piperine via autophagy and senescence signaling pathways in NB4 and MOLT-4 cells. The MTT assay results demonstrated that piperine significantly decreased the viability of NB4 and MOLT-4 cells. Piperine induced autophagy by increasing LC3, Beclin-1 and ULK1 and decreasing mTOR and NF-κB1 expression in NB4 and MOLT-4 cells. In addition, piperine increased senescence-associated beta-galactosidase fluorescence intensity by increasing p21 and IL-6 expression while decreasing CDK2 expression in NB4 and MOLT-4 cells. In conclusion, our study provides additional information about the induction of autophagy and senescence by piperine in acute leukemia.
The anti-inflammatory effect of a magnoliae cortex and Zea mays L. extract mixture in a canine model of ligature-induced periodontitis
Authors: Kim Se Eun , Hwang Sun Young , Park Yong Ho , Davis William C. , Park Kun Taek
Published: September 2024

Background

Periodontitis is common in dogs. It is characterized by destruction of the supporting tissues of the teeth due to the host-immune response triggered by plaque. Magnoliae cortex and Zea mays L. extract showed anti-inflammatory and anti-microbial effects, respectively. This study aimed to evaluate improvement in periodontitis following the administration of Magnoliae cortex and Zea mays L. extract in dogs. Periodontitis was experimentally induced in 10 beagle dogs. Five dogs were administered 40 mg of Magnoliae cortex extract and 20 mg of Zea mays L. extract orally once per day for 2 months (MZ group), whereas the other group received empty gelatin capsules (control group). Periodontal clinical parameters, complete blood count, serum chemistry parameters, and tissue inflammatory cytokines and chemokine expression were assessed before and after combined oral extracts administration.

Results

The complete blood count and serum chemistry results of all dogs were within normal ranges. Gingival inflammation in MZ group was significantly better than that in the control group at 4 and 8 weeks post-medication (PM; p < 0.05). The periodontal pocket depth and clinical attachment loss at 8 weeks PM in the MZ group were significantly lower than the baseline values (p < 0.05). The incidence of bleeding on probing in the MZ group was significantly lower than that in the control group at 4 weeks PM (p < 0.05). Throughout the medication period, the percentages of CD4 + and CD8 + T cells were higher and lower, respectively, in the MZ group. However, these differences were only significant at 8 weeks PM. The expression of the inflammatory cytokines IL-1β, IL-6, IL-17, and TNF-α and the chemokine IL-8 in the inflamed tissues was lower in the MZ group, and the two groups showed a significant difference in TNF-α expression.

Conclusions

Combined administration of Magnoliae cortex and Zea mays L. extract improved the clinical symptoms of periodontal disease in dogs. This beneficial effect may be partly due to the inhibitory effects of these extracts on the inflammatory response.
Localized delivery of therapeutics impact laryngeal mechanics, local inflammatory response, and respiratory microbiome following upper airway intubation injury in swine
Authors: Gonzales Gabriela , Malka Ronit , Marinelli Lisa M. , Lee Christine M. , Cook Stacy , Miar Solaleh , Dion Gregory R. , Guda Teja
Published: September 2024

Background

Laryngeal injury associated with traumatic or prolonged intubation may lead to voice, swallow, and airway complications. The interplay between inflammation and microbial population shifts induced by intubation may relate to clinical outcomes. The objective of this study was to investigate laryngeal mechanics, tissue inflammatory response, and local microbiome changes with laryngotracheal injury and localized delivery of therapeutics via drug-eluting endotracheal tube.

Methods

A simulated traumatic intubation injury was created in Yorkshire crossbreed swine under direct laryngoscopy. Endotracheal tubes electrospun with roxadustat or valacyclovir- loaded polycaprolactone (PCL) fibers were placed in the injured airway for 3, 7, or 14 days (n = 3 per group/time and ETT type). Vocal fold stiffness was then evaluated with normal indentation and laryngeal tissue sections were histologically examined. Immunohistochemistry and inflammatory marker profiling were conducted to evaluate the inflammatory response associated with injury and ETT placement. Additionally, ETT biofilm formation was visualized using scanning electron microscopy and micro-computed tomography, while changes in the airway microbiome were profiled through 16S rRNA sequencing.

Results

Laryngeal tissue with roxadustat ETT placement had increasing localized stiffness outcomes over time and histological assessment indicated minimal epithelial ulceration and fibrosis, while inflammation remained severe across all timepoints. In contrast, vocal fold tissue with valacyclovir ETT placement showed no significant changes in stiffness over time; histological analysis presented a reduction in epithelial ulceration and inflammation scores along with increased fibrosis observed at 14 days. Immunohistochemistry revealed a decline in M1 and M2 macrophage markers over time for both ETT types. Among the cytokines, IL-8 levels differed significantly between the roxadustat and valacyclovir ETT groups, while no other cytokines showed statistically significant differences. Additionally, increased biofilm formation was observed in the coated ETTs with notable alterations in microbiota distinctive to each ETT type and across time.

Conclusion

The injured and intubated airway resulted in increased laryngeal stiffness. Local inflammation and the type of therapeutic administered impacted the bacterial composition within the upper respiratory microbiome, which in turn mediated local tissue healing and recovery.
Human IL-22 receptor-targeted small protein antagonist suppress murine DSS-induced colitis
Authors: Kuchař Milan , Sloupenská Kristýna , Rašková Kafková Leona , Groza Yaroslava , Škarda Jozef , Kosztyu Petr , Hlavničková Marie , Mierzwicka Joanna M. , Osička Radim , Petroková Hana , Walimbwa Stephen I. , Bharadwaj Shiv , Černý Jiří , Raška Milan , Malý Petr
Published: October 2024

Background

Human interleukin-22 (IL-22) is known as a “dual function” cytokine that acts as a master regulator to maintain homeostasis, structural integrity of the intestinal epithelial barrier, and shielding against bacterial pathogens. On the other hand, the overexpression of IL-22 is associated with hyper-proliferation and recruitment of pathologic effector cells, leading to tissue damage and chronic inflammation in specific diseases including inflammatory bowel disease (IBD). To study a role of IL-22-mediated signaling axis during intestinal inflammation, we generated a set of small protein blockers of IL-22R1 and verified their inhibitory potential on murine model of colitis.

Methods

We used directed evolution of proteins to identify binders of human IL-22 receptor alpha (IL-22R1), designated as ABR ligands. This approach combines the assembly of a highly complex combinatorial protein library derived from small albumin-binding domain scaffold and selection of promising protein variants using ribosome display followed by large-scale ELISA screening. The binding affinity and specificity of ABR variants were analyzed on transfected HEK293T cells by flow cytometry and LigandTracer. Inhibitory function was further verified by competition ELISA, HEK-Blue IL-22 reporter cells, and murine dextran sulfate sodium (DSS)-induced colitis.

Results

We demonstrate that ABR specifically recognizes transgenic IL-22R1 expressed on HEK293T cells and IL-22R1 on TNFα/IFNγ-activated HaCaT cells. Moreover, some ABR binders compete with the IL-22 cytokine and function as IL-22R1 antagonists in HEK-Blue IL22 reporter cells. In a murine model of DSS-induced acute intestinal inflammation, daily intraperitoneal administration of the best IL-22R1 antagonist, ABR167, suppressed the development of clinical and histological markers of colitis including prevention of mucosal inflammation and architecture deterioration. In addition, ABR167 reduces the DSS-induced increase in mRNA transcript levels of inflammatory cytokines such as IL-1β, IL-6, IL-10, and IL-17A.

Conclusions

We developed small anti-human IL-22R1 blockers with antagonistic properties that ascertain a substantial role of IL-22-mediated signaling in the development of intestinal inflammation. The developed ABR blockers can be useful as a molecular clue for further IBD drug development.
Artificial intelligence driven definition of food preference endotypes in UK Biobank volunteers is associated with distinctive health outcomes and blood based metabolomic and proteomic profiles
Authors: Navratilova Hana F. , Whetton Anthony D. , Geifman Nophar
Published: October 2024

Background

Specific food preferences can determine an individual’s dietary patterns and therefore, may be associated with certain health risks and benefits.

Methods

Using food preference questionnaire (FPQ) data from a subset comprising over 180,000 UK Biobank participants, we employed Latent Profile Analysis (LPA) approach to identify the main patterns or profiles among participants. blood biochemistry across groups/profiles was compared using the non-parametric Kruskal–Wallis test. We applied the Limma algorithm for differential abundance analysis on 168 metabolites and 2923 proteins, and utilized the Database for Annotation, Visualization and Integrated Discovery (DAVID) to identify enriched biological processes and pathways. Relative risks (RR) were calculated for chronic diseases and mental conditions per group, adjusting for sociodemographic factors.

Results

Based on their food preferences, three profiles were termed: the putative Health-conscious group (low preference for animal-based or sweet foods, and high preference for vegetables and fruits), the Omnivore group (high preference for all foods), and the putative Sweet-tooth group (high preference for sweet foods and sweetened beverages). The Health-conscious group exhibited lower risk of heart failure (RR = 0.86, 95%CI 0.79–0.93) and chronic kidney disease (RR = 0.69, 95%CI 0.65–0.74) compared to the two other groups. The Sweet-tooth group had greater risk of depression (RR = 1.27, 95%CI 1.21–1.34), diabetes (RR = 1.15, 95%CI 1.01–1.31), and stroke (RR = 1.22, 95%CI 1.15–1.31) compared to the other two groups. Cancer (overall) relative risk showed little difference across the Health-conscious, Omnivore, and Sweet-tooth groups with RR of 0.98 (95%CI 0.96–1.01), 1.00 (95%CI 0.98–1.03), and 1.01 (95%CI 0.98–1.04), respectively. The Health-conscious group was associated with lower levels of inflammatory biomarkers (e.g., C-reactive Protein) which are also known to be elevated in those with common metabolic diseases (e.g., cardiovascular disease). Other markers modulated in the Health-conscious group, ketone bodies, insulin-like growth factor-binding protein (IGFBP), and Growth Hormone 1 were more abundant, while leptin was less abundant. Further, the IGFBP pathway, which influences IGF1 activity, may be significantly enhanced by dietary choices.

Conclusions

These observations align with previous findings from studies focusing on weight loss interventions, which include a reduction in leptin levels. Overall, the Health-conscious group, with preference to healthier food options, has better health outcomes, compared to Sweet-tooth and Omnivore groups.

Graphical Abstract
An efficient multiplex approach to CRISPR/Cas9 gene editing in citrus
Authors: Sagawa Cintia H. D. , Thomson Geoffrey , Mermaz Benoit , Vernon Corina , Liu Siqi , Jacob Yannick , Irish Vivian F.
Published: September 2024

CRISPR/Cas9-mediated gene editing requires high efficiency to be routinely implemented, especially in species which are laborious and slow to transform. This requirement intensifies further when targeting multiple genes simultaneously, which is required for genetic screening or more complex genome engineering. Species in the Citrus genus fall into this category. Here we describe a series of experiments with the collective aim of improving multiplex gene editing in the Carrizo citrange cultivar using tRNA-based sgRNA arrays. We evaluate a range of promoters for their efficacy in such experiments and achieve significant improvements by optimizing the expression of both the Cas9 endonuclease and the sgRNA array. In the case of the former we find the UBQ10 or RPS5a promoters from Arabidopsis driving the zCas9i endonuclease variant useful for achieving high levels of editing. The choice of promoter expressing the sgRNA array also had a large impact on gene editing efficiency across multiple targets. In this respect Pol III promoters perform especially well, but we also demonstrate that the UBQ10 and ES8Z promoters from Arabidopsis are robust alternatives. Ultimately, this study provides a quantitative insight into CRISPR/Cas9 vector design that has practical application in the simultaneous editing of multiple genes in Citrus, and potentially other eudicot plant species.
Variation in forest root image annotation by experts, novices, and AI
Authors: Handy Grace , Carter Imogen , Mackenzie A. Rob , Esquivel-Muelbert Adriane , Smith Abraham George , Yaffar Daniela , Childs Joanne , Arnaud Marie
Published: October 2024

Background

The manual study of root dynamics using images requires huge investments of time and resources and is prone to previously poorly quantified annotator bias. Artificial intelligence (AI) image-processing tools have been successful in overcoming limitations of manual annotation in homogeneous soils, but their efficiency and accuracy is yet to be widely tested on less homogenous, non-agricultural soil profiles, e.g., that of forests, from which data on root dynamics are key to understanding the carbon cycle. Here, we quantify variance in root length measured by human annotators with varying experience levels. We evaluate the application of a convolutional neural network (CNN) model, trained on a software accessible to researchers without a machine learning background, on a heterogeneous minirhizotron image dataset taken in a multispecies, mature, deciduous temperate forest.

Results

Less experienced annotators consistently identified more root length than experienced annotators. Root length annotation also varied between experienced annotators. The CNN root length results were neither precise nor accurate, taking ~ 10% of the time but significantly overestimating root length compared to expert manual annotation (p = 0.01). The CNN net root length change results were closer to manual (p = 0.08) but there remained substantial variation.

Conclusions

Manual root length annotation is contingent on the individual annotator. The only accessible CNN model cannot yet produce root data of sufficient accuracy and precision for ecological applications when applied to a complex, heterogeneous forest image dataset. A continuing evaluation and development of accessible CNNs for natural ecosystems is required.
A high-flexion design total knee prosthesis: a ten to twelve-year follow-up study
Authors: Kim Man Soo , Choi Keun Young , Hur Jae Hyeong , In Yong
Published: September 2024

Background

The purpose of this study was to investigate the clinical and radiographic outcomes and to determine the survivorship of a high-flexion design total knee arthroplasty (TKA) prosthesis, the LOSPA knee system, over a follow-up period of 10–12 years.

Methods

The study included 386 patients (503 TKAs) who were treated with TKA from 2011 to 2013 (follow-up period 10–12 years).The patients were assessed clinically using range of motion (ROM) of the knee, the Knee Society scoring system (KSS), and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). For radiographic analysis, the positions of femoral and tibial implants as α, β, γ, and δ angles, hip knee ankle (HKA) angle, and radiolucent lines were used. Kaplan–Meier survival analysis was performed.

Results

Mean ROM improved significantly from the preoperative baseline of 117.3° to 126.5° at the final follow-up (p < 0.001). The mean KSS and WOMAC scores also both showed significant improvement after surgery (all p < 0.001). A non-progressive radiolucent line less than 2 mm was observed in 23 cases (4.7%). Nine patients underwent revision surgery on the knee during the follow-up period. Revision surgery was performed on four patients due to aseptic loosening, three patients due to infection, one patient due to ankylosis, and one patient due to instability. When the endpoint of survival was the entire surgical cases, the survival rate was 96.2%. The survival rate, with revision for any reason as the endpoint, was 97.2%, and 97.8% for aseptic causes.

Conclusions

The LOSPA knee system, a high-flexion design total knee prosthesis, showed excellent long-term survivorship and improvements in clinical outcomes at 10- to 12-year follow-up.
Midterm clinical and radiological outcomes of arthrogryposis-associated clubfoot treated with the Ponseti method: a retrospective observational study and comprehensive literature review
Authors: Berger Nina , Forkl Hans , Heimkes Bernhard , Frimberger Vincent , Wagner Ferdinand , Hildebrand Frank , Delbrück Heide
Published: September 2024

Background

The treatment results of the Ponseti method for arthrogrypotic clubfoot have been described in only a few case series. Further evaluations are necessary.

Methods

Children from two German paediatric orthopaedic hospitals with arthrogryposis-associated clubfoot treated with the Ponseti method between 2004 and 2011 and who were at least five years of age at their last follow-up were retrospectively evaluated. The endpoints were the clinical foot position, necessary surgeries during the follow-up period and radiological constellations. A comprehensive literature review was conducted after a systematic literature search.

Results

Seventeen patients (47% with amyoplasia [AP] and 53% with distal arthrogryposis [DA]) met the inclusion criteria. Thirty-one feet were evaluated. The period between the treatment start and the last follow-up examination covered 8.9 ± 2.5 years. After the last cast removal within the initial Ponseti cast series, 74% of the clinical results were good to excellent. However, the clinical outcomes in the patients with AP were significantly worse. Overall, in 23 feet (74%), at least one major surgery at the age of 2.9 ± 2.2 years was necessary during the clinical course. Major surgeries were much more frequent on the feet of the patients with AP than with DA. Lateral X-rays showed normal age-appropriate radiological angles in 4% of the feet, hindfoot equinus in 19%, under-corrected hindfoot in 44%, under-corrected clubfoot in 26% and rocker bottom deformity in 7%. The radiological residual deformities in AP were much more severe than in DA (p = 0.042). Most of the studies reviewed (11 case series, 144 patients) reported high initial clinical correction rates, followed by high recurrence rates and the need for further surgeries.

Conclusion

About a quarter of the arthrogrypotic patients benefited from the Ponseti therapy without further major surgery. However, the clinically observed high initial correction rate after Ponseti therapy of arthrogrypotic clubfoot was not accompanied by a correction of the bony foot position in the X-rays. The feet of the patients with DA had better outcomes than those of the patients with AP. Therefore, in outcome studies, a clear distinction between patients with AP and those with DA is necessary.