bluuebunny/crossref_metadata_2025 huggingface dataset:
Reliability of Gordon Lateral Rotation Percentage and Prabhakar Percentage of Metaphyseal Overhang for Pediatric Supracondylar Humerus Fracture; Is it Clinically Reliable for John Hopkins Classification Coronal Fracture Subtypes?
Authors: Şahbat Yavuz , Bekiroğlu Gülnaz Nural , Çat Görkem , Gündoğdu Mert , Ağirdil Yücel , Çayir Hüseyin , Onay Tolga , Akgülle Ahmet Hamdi
Published: September 2023

Background:

Rotational malalignment is a common problem in pediatric supracondylar humerus fractures (SCHF). Several techniques have been described to evaluate the true rotation value. Although the Prabhakar and Gordon techniques are used frequently, their superiority to each other in terms of measurement quality is unknown.

Questions/Purposes:

The aim of this study was to investigate the clinical compatibility of the 2 techniques and to evaluate whether they are suitable for all subtypes.

Methods:

This cross-sectional study included 40 patients with SCHF (including subtypes; Typical, Medial Oblique, Lateral Oblique, and High fracture pattern). The Gordon lateral rotation percentage and Prabhakar percentage of metaphyseal overhang were measured twice by 4 experienced Orthopedics and Traumatology surgeons at 8-week intervals. The interobserver and intraobserver reliability were examined using the intraclass correlation coefficient.

Results:

The interobserver reliability for Gordon and Prabhakar technique was 0.816 and 0.762 for the first measurement and 0.811 and 0.811 for the second measurement, respectively.

The medial oblique fracture pattern was determined to have the best interobserver agreement among the subtypes. The result was excellent for the medial and lateral oblique subtypes, good for the typical fracture pattern, and fair for the high fracture pattern. The intraobserver reliability for Gordon and Prabhakar technique was excellent, 0.924 and 0.922, respectively.

Conclusion:

The main finding of this study was that the Gordon and Prabhakar techniques have similar interobserver and intraobserver reliability. Although the Gordon technique tends to have higher interobserver reliability, the difference was clinically insignificant. These measurements should not be relied upon in cases of SCHF with a high fracture pattern because of the different anatomic features of that region.

Level of Evidence:

Level III.
A Modified Approach for Arthroscopic Excision of Dorsal Midcarpal Ganglion Cysts Using Radiocarpal Portals
Authors: Lee Kun-Han , Huang Hui-Kuang , Wang Jung-Pan
Published: September 2023

Wrist arthroscopy could be a treatment option for dorsal ganglion cysts. To achieve a thorough dorsal capsulectomy for the removal of midcarpal ganglion cysts, it is commonly necessary to combine both the radiocarpal and midcarpal portals. We present a modified method using radiocarpal portals only for arthroscopically excising dorsal midcarpal ganglion cysts. No extra midcarpal portals are necessary, and the method potentially generates satisfactory results.
Melanoma-specific survival in worse in the elderly: a multicentric cohort study
Authors: Segura Sonia , Podlipnik Sebastian , Boada Aram , Martí Rosa M , Sabat Mireia , Yélamos Oriol , Zarzoso-Muñoz Inés , Azón-Masoliver Antoni , López-Castillo Daniel , Solà Joaquim , Baliu-Piqué Carola , Galvany-Rossell Loida , Pasquali Paola , Just-Sarobé Miquel , Duran Xavier , Carrera Cristina , Richarz Nina A. , Pujol Ramon M. , Malvehy Josep , Puig Susana ,   on behalf of the Network of Melanoma Centres of Catalonia
Published: September 2023

We aimed to characterise cutaneous melanoma in the elderly and determine its association with poorer prognosis. We studied a prospective cohort of the melanoma population in Catalonia between 2012 and 2016. We compared young patient group (<75 years old) with elderly patient group (≥75 years old). We included 3009 patients (52.5% women) from 14 centres, with a mean age at diagnosis of 61.1 years. In the ≥75-year-old group there was a predominance of men (53.9% vs. 45.5%, P < 0.001), melanoma was more frequently located in the head and neck area (37.7% vs. 15.5%, P < 0.001) and lentigo maligna melanoma subtype was significantly more frequent (31.4% vs. 11.6%, P < 0.001), as were nodular melanoma and acral lentiginous melanoma (P < 0.001). In older people, Breslow index, the presence of ulceration and mitotic rate were higher than in younger people. Kaplan–Meier survival curves showed longer melanoma specific survival (MSS) and melanoma-free survival (MFS) in <75-year-old group compared to the elderly group. Cox regression models demonstrated reduced MSS in patients ≥75 years regardless of gender, location, IB, ulceration and lymph node status at diagnosis (HR 1.54, P = 0.013) whereas MFS was not independently associated with elderly when head and neck location was considered. Age appears to be an independent risk factor for MSS but not for MFS. Worse melanoma prognosis in elderly could be explained by factors unrelated to the tumour, such as age-related frailty and comorbidities that limit the access to systemic treatments and, eventually, age-related immune dysfunction.
Safety of immune checkpoint inhibitors after proton beam therapy in head and neck mucosal melanoma: a case series
Authors: Uematsu Mao , Nakajima Hiromichi , Hosono Ako , Kiyohara Hikari , Hirota Akira , Takahashi Nobuyuki , Fukuda Misao , Kusuhara Shota , Nakao Takehiro , Funasaka Chikako , Kondoh Chihiro , Harano Kenichi , Matsubara Nobuaki , Naito Yoichi , Akimoto Tetsuo , Mukohara Toru
Published: September 2023

Proton beam therapy (PBT) has shown promising efficacy in treating locally advanced head and neck mucosal melanoma despite its poor prognosis. Although PBT may improve the efficacy of subsequent immune checkpoint inhibitors (ICIs), the safety of ICIs in patients who have previously received PBT has not been established. Hence, this study evaluated the safety of ICIs in patients who had recurrent mucosal melanoma after PBT. Between April 2013 and June 2022, we retrospectively reviewed the medical records of patients diagnosed with cutaneous or mucosal melanoma at the National Cancer Center Hospital East. Seven patients were treated with ICIs after their head and neck mucosal melanoma (HNMM) recurred after PBT. Four of the seven patients experienced grade immune-related adverse events (irAEs). Due to irAE in the irradiation field, two patients had grade 3 hypopituitarism. Other grade 3 or higher irAEs included an increase in serum alanine aminotransferase in two patients and gastritis in one, and two patients discontinued ICI due to the irAEs. All irAEs were resolved with appropriate management. Although administering ICIs after PBT may increase the risk of irAEs, especially in the irradiation field, they appear manageable. These findings could help in the development of a treatment strategy for locally advanced HNMM that includes PBT and subsequent ICIs.
A transcatheter “sandwich” valve-in-valve implantation for pure aortic regurgitation: a report of 2 cases
Authors: Chen Shasha , Lin Dawei , Qi Yiming , Zhou Daxin , Pan Wenzhi , Ge Junbo
Published: September 2023

The application of transcatheter aortic valve replacement (TAVR) for severe pure native aortic valve regurgitation (PNAR) remains limited. TAVR for PNAR using an off-label device is associated with acceptable procedural success but increased early mortality. For performing TAVR for PNAR patients, appropriate anatomy, especially a relatively small aortic annulus, is a necessary condition for successful procedure, and large aortic annulus is generally excluded. Here, we report using a new transcatheter “sandwich” valve-in-valve implantation technique with commercially available devices for treating two cases of PNAR, including one with a extremely large aortic annulus (namely aortic annulus perimeter over 91.1 mm, respectively, according to the industry instructions VitaFlow®). The conditions of both patients improved, and there were no complications during the follow-up periods. The new transcatheter “sandwich” valve-in-valve implantation technique using the commercially available self-expanding devices could be an option for treating PNAR patients with an extremely large annulus at high risk for surgery. This technique can also be an effective remedy for the first valve to be placed too high and jump up to the ascending aorta.
A multi-device robotic-assisted PCI system: a proof-of concept study for left main bifurcation stenting with culotte technique in a porcine model
Authors: Han Wenzheng , Wang Ming , Guan Shaofeng , Gan Qian , Fang Weiyi , Xia Kun , Qu Xinkai
Published: September 2023

Background and purpose:

Robotic-assisted percutaneous coronary intervention (PCI) has been increasingly used for simple lesion. For complex lesions, extensive manual intervention is still required. This study aims to verify the stability and safety of this robot system in complex lesion under fifth-generation (5G) network before clinical trial.

Methods:

We developed a robotic system that allows simultaneous remote control of multiple devices using a 5G wireless network. The key feature of the system is a bionic thumb along with two-bionic forefingers. The system was tested in eight pigs (six over 18.3 km and two over 1,100 km). Two stents were placed in the left main bifurcation using the culotte technique. All procedures, barring device loading onto the robot system, including manipulation of the guiding catheter, wire adjustments, stent or balloon positioning, and notably the final kissing step, were conducted remotely.

Results:

The rate of procedure success was 100%, with no device-related complications. In comparison to short-distance remote control, the delay with long-distance remote control was minimal (90.9 ± 1.5 vs. 81.5 ± 2.7 ms for command data transmission; 163.2 ± 1.3 vs. 161.0 ± 1.4 ms for image transmission). The procedure time was shorter when using two pairs versus a single pair of bionic fingers (104.3 ± 10.2 vs. 126.0 ± 3.9 min), primarily due to less time needed for device loading and exchange (33.1 ± 4.2 vs. 56.1 ± 4.0 min).

Conclusions:

With the 5G network, long distance was not a significant barrier for robotic-assisted PCI for chronic total occlusion. A design of the independent bionic finger module enabled final kissing balloon inflation with reduced requirement for manual intervention. Whether the system could be used beyond left main bifurcation lesions requires further investigation.
The Development of a Systems-Level Approach to Address Adolescent Access to Health Care
Authors: Wilson Kelly L. , Garney Whitney R. , Garcia Kristen M. , Esquivel Christi H. , Ajayi Kobi V. , Flores Sara A. , Curran Laurel
Published: September 2023

Most evidence-based interventions in adolescent sexual and reproductive health and mental health remain largely aimed at individual-level outcomes and do not conceptualize adolescent health within a social-ecological model. Interventions to affect policy, systems, and environmental change offer potential for sustained population impact. The current initiative used an innovation framework to develop a novel systems-level approach to address adolescent access to health care. The Framework for Public Health Innovation provided an approach to develop a novel intervention. Confident Teen is a systems-level intervention that creates the opportunity, through organizational policy change, to increase adolescents' access to confidential sexual and reproductive health services through organizational policies. Gaps in adolescents' access to health care services allowed for a systems-level approach to be designed through an adolescent pregnancy prevention innovation initiative. Confidentiality is a right and critical component to their health care; therefore, a policy and conversation between provider and patient is a prioritized component of the novel intervention.
Impact of octreotide on sodium level in cirrhotic inpatients with hyponatremia: a retrospective study
Authors: Ismail Bahaaeldeen , Charnigo Richard , Ali Syed Mohammad , Alkhairi Baker , Benrajab Karim , Singh Harjinder , Castro Fernando J.
Published: September 2023

Objective

Octreotide could increase serum sodium in cirrhotics with hyponatremia by counteracting splanchnic vasodilation. Current supporting data is limited to case reports and series. The aim of the study is to assess the effect of octreotide on serum sodium in cirrhotic inpatients with hyponatremia compared with controls.

Methods

This is a retrospective study including adult inpatients with cirrhosis, admitted for ≥5 days with Na <133 at baseline. We excluded those receiving other vasoconstrictor infusions, hypertonic saline, tolvaptan or dialysis. Controls represented an equal number of inpatients with cirrhosis not receiving octreotide. Sodium changes on days 5, 7 and 10 were evaluated with multivariable adjustment.

Results

Each group consisted of 156 patients. The octreotide subjects had more cirrhosis complications. Baseline sodium was lower in the octreotide group, and their change in sodium at day 5 was higher (6.6 ± 5.6 vs. 3.5 ± 5.3; P < 0.001). Significant differences were also noted on days 7 and 10 (7.84 ± 6.76 vs. 4.33 ± 6.2 and 7.99 ± 6.72 vs. 5.2 ± 6.56, respectively). The impact of octreotide was lessened but remained significant (P = 0.019) in a mixed model adjusting for baseline sodium, creatinine, requirement of paracentesis, midodrine, albumin and fresh frozen plasma. More octreotide patients achieved hyponatremia resolution (55.1% vs. 42.3%; P = 0.031), but significance was not preserved in multivariate logistic regression.

Conclusion

Octreotide administration is associated with an increase in serum sodium among inpatient cirrhotics with hyponatremia, even after accounting for confounders. Prospective randomized controlled trials are warranted.
Post-COVID pneumatocele, a rare entity managed surgically: a case series
Authors: Wahab Rida , Sohail Abdul A. , Khalid Rifsha , Sundardas Rita , Fatimi Saulat H.
Published: September 2023

Introduction:

A pulmonary pneumatocele is a thin air filled cavitatory lesion that develops within the lung parenchyma. It is a unique, rarely occurring complication of COVID-19 pneumonia, most commonly detected by chest radiographs and computed tomography scans.

Case presentation:

The authors present a case series of four separate cases, all of which had suffered from COVID pneumonia, and now developed symptomatic pneumatocele. Two patients out of the four had also developed pneumothorax for which a tube thoracostomy was done, which is an infrequent complication of pneumatocele. One had an accompanying fungal infected loculated effusion. In all of these patients surgical management was approached as a treatment modality with three patients requiring bullectomy and one requiring lobectomy since image-guided drainage technique is not widely available in our resource-limited setting.

Discussion:

A pneumatocele, also called a pseudocyst, due to the absence of epithelial lining, is a thin-walled cystic cavity, filled with air that develops in the pulmonary interstitium. The most common cause is iatrogenic injury, due to prolonged mechanical ventilation. Pneumatoceles are usually asymptomatic and resolve spontaneously; however, image-guided drainage and surgical management can be opted for, in the presence of the complications.

Conclusion:

From our case report, it can be concluded that the surgical approach is relatively safe and effective, with increased survival benefits, especially in those patients who develop complicated pneumatocele.
Patient survival prediction in locally advanced cervical squamous cell carcinoma using MRI-based radiomics: retrospective cohort study
Authors: Bseiso Anan , Saqib Muhammad , Saigol Muhammad Sherdil , Rehman Aribah , Sare Almatou , Yagoub Ahmed Elmustafa , Mumtaz Hassan
Published: September 2023

Cervical cancer is a major health concern for women, ranking as the fourth most common cancer and a significant cause of cancer-related deaths worldwide. To enhance prognostic predictions for locally advanced cervical squamous cell carcinoma, we conducted a study utilizing radiomics features extracted from pretreatment magnetic resonance images. The goal was to predict patient survival and compare the predictive value of these features with clinical traits and the 2018 International Federation of Obstetrics and Gynecology (FIGO) staging system. In our retrospective cohort study, we included 500 patients with confirmed cervical squamous cell carcinoma ranging from FIGO stages IIB to IVA under the 2018 staging system. All patients underwent pelvic MRI with diffusion-weighted imaging before receiving definitive curative concurrent chemoradiotherapy. The results showed that the combination model, incorporating radiomics scores and clinical traits, demonstrated superior predictive accuracy compared to the widely used 2018 FIGO staging system for both progression-free and overall survival. Age was identified as a significant factor influencing survival outcomes. Additionally, primary tumour invasion stage, tumour maximal diameter, and the location of lymph node metastasis were found to be important predictors of progression-free survival, while primary tumour invasion stage and lymph node metastasis position individually affected overall survival. During the follow-up period, a portion of patients experienced disease-related deaths or tumour progression/recurrence in both sets. The radiomics-score significantly enhanced prediction ability, providing valuable insights for guiding personalized therapy approaches and stratifying patients into low-risk and high-risk categories for progression-free and overall survival. In conclusion, our study demonstrated the potential of radiomics features as a valuable addition to existing clinical tools like the FIGO staging system, offering promising advancements in managing locally advanced cervical squamous cell carcinoma.
Mycobacterium tuberculosis-induced monocyte transcriptional responses associated with resistance to tuberculin skin test/interferon-γ release assay conversion in people with HIV
Authors: Hong Hyejeong , Dill-Mcfarland Kimberly A. , Benson Basilin , Simmons Jason D. , Peterson Glenna J. , Benchek Penelope , Stein Catherine M. , Boom W. Henry , Mayanja-Kizza Harriet , Hawn Thomas R.
Published: September 2023

Objective:

To determine whether Mycobacterium tuberculosis (Mtb)-induced monocyte transcriptional responses differ in people with HIV (PWH) who do (RSTR) or do not (LTBI) resist tuberculin skin test/interferon-γ (IFN-γ) release assay (TST/IGRA) conversion after exposure.

Design:

We compared ex-vivo Mtb-induced monocyte transcriptional responses in a Ugandan tuberculosis (TB) household contact study of RSTR and LTBI individuals among PWH.

Methods:

Monocytes were isolated from peripheral blood mononuclear cells from 19 household contacts of pulmonary TB patients, and their transcriptional profiles were measured with RNA-Seq after a 6 h infection with Mtb (H37Rv) or media. Differentially expressed genes (DEGs) were identified by a linear mixed effects model and pathways by gene set enrichment analysis that compared RSTR and LTBI phenotypes with and without Mtb stimulation.

Results:

Among PWH, we identified 8341 DEGs that were dependent on Mtb stimulation [false discovery rate (FDR) <0.01]. Of these, 350 were not significant (FDR >0.2) in individuals without HIV. Additionally, we found 26 genes that were differentially expressed between RSTR and LTBI monocytes in PWH, including 20 which were Mtb-dependent (FDR <0.2). In unstimulated monocytes, several gene sets [TGF-β signaling, TNF-α signaling via NF-κB, NOTCH signaling, coagulation, and epithelial mesenchymal transition (EMT)] were enriched in RSTR relative to LTBI monocytes (FDR <0.1). These patterns were not observed in individuals without HIV.

Conclusion:

RSTR monocytes in PWH show different gene expressions in response to Mtb infection when compared with those with LTBI and RSTR without HIV. These differential expression patterns are enriched in inflammatory pathways.
Kidney Donation After Circulatory Death Using Thoracoabdominal Normothermic Regional Perfusion: The Largest Report of the United States Experience
Authors: Zhou Alice L. , Leng Albert , Ruck Jessica M. , Akbar Armaan F. , Desai Niraj M. , King Elizabeth A.
Published: September 2023

Background.

Thoracoabdominal normothermic regional perfusion (TA-NRP) has been increasingly used for donation after circulatory death (DCD) procurements in the United States. We present the largest report of outcomes of kidney transplants performed using DCD donor grafts perfused with TA-NRP.

Methods.

Adult DCD kidney transplants between 2020 and 2022 in the United Network for Organ Sharing database were included. Donors with ≥50 min between asystole and aortic cross-clamp time in which the heart was also transplanted were considered TA-NRP donors. All other donors were considered direct recovery donors. Multivariable regressions were used to assess delayed graft function, as well as posttransplant survival and all-cause graft failure at 30, 90, and 180 d. A propensity-matched analysis of cohorts matched on donor Kidney Donor Profile Index was performed.

Results.

Of the 16 140 total DCD kidney transplants performed during the study period, 306 (1.9%) used TA-NRP. TA-NRP donors were younger (P < 0.001) and had lower Kidney Donor Profile Index (P < 0.001) compared with direct recovery donors. Recipients receiving grafts recovered using TA-NRP were younger (P < 0.001) and more likely to be blood group O (P < 0.001). Transplants using TA-NRP had lower likelihood of delayed graft function (adjusted odds ratio 0.22 [95% confidence interval, 0.15-0.31], P < 0.001) but similar 180-d survival (P = 0.8) and all-cause graft failure (P = 0.3) as transplants using direct recovery grafts. These inferences were unchanged on propensity-matched analysis.

Conclusions.

Our results demonstrate that kidney transplants using TA-NRP DCD allografts have positive short-term mortality and graft survival outcomes, with significantly decreased rates of delayed graft function compared with direct recovery DCD grafts.
‘The illness isn’t the end of the road’ - Patient perspectives on the initiation of and early participation in a multi-disease, community-based exercise programme
Authors: Regan-Moriarty Joanne , Hardcastle Sarah , McCallion Maire , Youell Azura , Collery Audrey , McCarren Andrew , Moyna Niall , Kehoe Brona
Published: September 2023

Background

Exercise is the cornerstone of cardiac rehabilitation (CR). Hospital-based CR exercise programmes are a routine part of clinical care and are typically 6-12 weeks in duration. Following completion, physical activity levels of patients decline. Multi-disease, community-based exercise programmes (MCEP) are an efficient model that could play an important role in the long-term maintenance of positive health behaviours in individuals with cardiovascular disease (CVD) following their medically supervised programme.

Aim

To explore patients experiences of the initiation and early participation in a MCEP programme and the dimensions that facilitate and hinder physical activity engagement.

Methods

Individuals with established CVD who had completed hospital-based CR were referred to a MCEP. The programme consisted of twice weekly group exercise classes supervised by clinical exercise professionals. Those that completed (n=31) an initial 10 weeks of the programme were invited to attend a focus group to discuss their experience. Focus groups were transcribed and analysed using reflexive thematic analysis.

Results

Twenty-four (63% male, 65.5±6.12yrs) patients attended one of four focus groups. The main themes identified were ‘Moving from Fear to Confidence’, ‘Drivers of Engagement,’ and ‘Challenges to Keeping it (Exercise) Up’.

Conclusion

Participation in a MCEP by individuals with CVD could be viewed as a double-edged sword. Whilst the programme clearly provided an important transition from the clinical to the community setting, there were signs it may breed dependency and not effectively promote independent exercise. Another novel finding was the use of social comparison that provided favourable valuations of performance and increased exercise confidence.
Macrophage-fibroblast crosstalk drives Arg1-dependent lung fibrosis via ornithine loading
Authors: Yadav Preeti , Ortega Javier Gómez , Tamaki Whitney , Chien Charles , Chang Kai-chun , Biswas Nivedita , Pan Sixuan , Nilsson Julia , Yin Xiaoyang , Bhattacharyya Aritra , Boostanpour Kaveh , Jujaray Tanay , Wang Jasper , Tsukui Tatsuya , Sheppard Dean , Li Baosheng , Maishan Mazharul , Taenaka Hiroki , Matthay Michael A. , Muramatsu Rieko , Maliskova Lenka , Ghosh Arnab , Eckalbar Walter L. , Molofsky Ari B. , Wolters Paul J. , Tamaki Stanley J. , Bivona Trever , Abate Adam R. , Wagner Allon , Tharp Kevin M. , Bhattacharya Mallar
Published: September 2023

Monocyte-derived macrophages recruited to injured tissues induce a maladaptive fibrotic response characterized by excessive production of collagen by local fibroblasts. Macrophages initiate this programming via paracrine factors, but it is unknown whether reciprocal responses from fibroblasts enhance profibrotic polarization of macrophages. We identify macrophage-fibroblast crosstalk necessary for injury-associated fibrosis, in which macrophages induced interleukin 6 (IL-6) expression in fibroblasts via purinergic receptor P2rx4 signaling, and IL-6, in turn, induced arginase 1 (Arg1) expression in macrophages. Arg1 contributed to fibrotic responses by metabolizing arginine to ornithine, which fibroblasts used as a substrate to synthesize proline, a uniquely abundant constituent of collagen. Imaging of idiopathic pulmonary fibrosis (IPF) lung samples confirmed expression ofARG1in myeloid cells, and arginase inhibition suppressed collagen expression in cultured precision-cut IPF lung slices. Taken together, we define a circuit between macrophages and fibroblasts that facilitates cross-feeding metabolism necessary for injury-associated fibrosis.
Explainable Machine Learning Reveals the Role of the Breast Tumor Microenvironment in Neoadjuvant Chemotherapy Outcome
Authors: Azimzade Youness , Haugen Mads Haugland , Tekpli Xavier , Steen Chloé B. , Fleischer Thomas , Kilburn David , Ma Hongli , Egeland Eivind Valen , Mills Gordon , Engebraaten Olav , Kristensen Vessela N. , Frigessi Arnoldo , Köhn-Luque Alvaro
Published: September 2023

Recent advancements in single-cell RNA sequencing (scRNA-seq) have enabled the identification of phenotypic diversity within breast tumor tissues. However, the contribution of these cell phenotypes to tumor biology and treatment response has remained less understood. This is primarily due to the limited number of available samples and the inherent heterogeneity of breast tumors. To address this limitation, we leverage a state-of-the-art scRNA-seq atlas and employ CIBER-SORTx to estimate cell phenotype fractions by de-convolving bulk expression profiles in more than 2000 samples from patients who have undergone Neoad-juvant Chemotherapy (NAC). We introduce a pipeline based on explainable Machine Learning (XML) to robustly explore the associations between different cell phenotype fractions and the response to NAC in the general population as well as different subtypes of breast tumors. By comparing tumor subtypes, we observe that multiple cell types exhibit a distinct association with pCR within each subtype. Specifically, Dendritic cells (DCs) exhibit a negative association with pathological Complete Response (pCR) in Estrogen Receptor positive, ER+, (Luminal A/B) tumors, while showing a positive association with pCR in ER-(Basal-like/HER2-enriched) tumors. Analysis of new spatial cyclic immunoflu-orescence data and publicly available imaging mass cytometry data showed significant differences in the spatial distribution of DCs between ER subtypes. These variations underscore disparities in the engagement of DCs within the tumor microenvironment (TME), potentially driving their divergent associations with pCR across tumor subtypes. Overall, our findings on 28 different cell types provide a comprehensive understanding of the role played by cellular compo-nents of the TME in NAC outcomes. They also highlight directions for further experimental investigations at a mechanistic level.
Clinically relevant orthotopic pancreatic cancer models for adoptive T cell therapy
Authors: Horvat Natalie K. , Karpovsky Isaac , Phillips Maggie , Wyatt Megan , Hall Margaret A. , Herting Cameron , Hammons Jacklyn , Mahdi Zaid , Moffitt Richard A. , Paulos Chrystal M. , Lesinski Gregory B.
Published: September 2023

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive tumor. Prognosis is poor and survival is low in patients diagnosed with this disease; ∼12% at 5 years. Immunotherapy, including adoptive T cell transfer therapy, has not impacted outcomes in PDAC patients, due in part to the hostile tumor microenvironment (TME) which limits T cell trafficking and persistence. We posit that murine models serve as useful tools to study the fate of T cell therapy. Currently, genetically engineered mouse models (GEMM) for PDAC are considered a “gold-standard” as they recapitulate many aspects of human disease. However, these models have limitations, including marked tumor variability across individual mice and cost of colony maintenance. We characterized the immunologic features and trafficking patterns of adoptively transferred T cells in orthotopic PDAC models using two mouse cell lines, KPC-Luc and MT-5, isolated from KPC-GEMM mouse models (KrasLSL-G12D/+p53-/-and KrasLSL-G12D/+p53LSL-R172H/+, respectively). The MT-5 orthotopic model best recapitulates the cellular and stromal features of the TME in the PDAC GEMM. In contrast, far more host immune cells infiltrate KPC-Luc tumors, which have less stroma. Albeit CD4+ T cells were similarly detected in MT-5 tumors compared to KPC-GEMM in mice. Interestingly, we found that CAR T cells redirected to recognize mesothelin on these tumors that signal via CD3σ and 41BB (Meso-41BBσ-CAR T cells) post antigen recognition infiltrated the tumors of mice bearing stroma-devoid KPC-Luc orthotopic tumors, but not MT-5 tumors. Our data establish for the first time a reproducible and realistic clinical system useful for modeling stroma-rich and stroma-devoid PDAC tumors. These models shall serve in-depth study of how to overcome barriers that limit anti-tumor activity of adoptively transferred T cells.
Neutrophil-fibroblast crosstalk drives immunofibrosis in Crohn’s disease through IFNα pathway
Authors: Gavriilidis Efstratios , Divolis Georgios , Natsi Anastasia-Maria , Kafalis Nikolaos , Kogias Dionysios , Antoniadou Christina , Synolaki Evgenia , Pavlos Evgenios , Koutsi Marianna A. , Didaskalou Stylianos , Tsironidou Victoria , Gavriil Ariana , Papadopoulos Vasileios , Agelopoulos Marios , Tsilingiris Dimitrios , Koffa Maria , Giatromanolaki Alexandra , Kouklakis Georgios , Ritis Konstantinos , Skendros Panagiotis
Published: September 2023

This study investigated the interaction between neutrophils and intestinal fibroblasts in Crohn’s disease (CD) immunofibrosis. Peripheral neutrophils, enriched-neutrophil extracellular traps (eNETs), serum, primary intestinal fibroblasts (PIFs) and intestinal biopsies were studied. Neutrophils’ RNA-sequencing, multi-cytokine profiling and cell-based functional assays at mRNA/protein level were performed. Compared to ulcerative colitis (UC), PIFs from CD patients displayed a distinct fibrotic phenotype characterized by negative Krüppel-like Factor-2 (KLF2) and increased cellular communication network factor-2 (CCN2) expression leading to collagen production. PIFs-derived IL-8 appears as a culprit chemoattractant of neutrophils in the intestine, where CD neutrophils were accumulated close to fibrotic lesions. Functionally, only CD neutrophilsviaeNETs can induce a CD-like phenotype in HI PIFs. High serum IFNα and IFΝ-responsive signature in neutrophils were observed in CD, distinguishing it from UC. Moreover, CD serum can stimulate the release of fibrogenic eNETs in an IFNα-dependent manner, suggesting the priming role of IFNα in circulating neutrophils. Inhibition of eNETs or JAK signaling in neutrophils or PIFs prevented the neutrophil-mediated fibrotic effect on PIFs. Furthermore, serum IFNα and transcripts of key IFN-signaling components in neutrophils were well-correlated with CD severity. This study reveals the role of IFNα/neutrophil/fibroblast axis in CD immunofibrosis, suggesting candidate biomarkers and therapeutic targets.
Molecular Landscape and Contemporary Prognostic Signatures of Gliomas
Authors: Ghosh Hia S. , Patel Ruchit V. , Woodward Eleanor , Greenwald Noah F. , Bhave Varun M. , Maury Eduardo A. , Cello Gregory , Hoffman Samantha E. , Li Yvonne , Gupta Hersh , Spurr Liam F. , Vogelzang Jayne , Touat Mehdi , Dubois Frank , Cherniack Andrew D. , Guo Xiaopeng , Tavakol Sherwin , Cioffi Gino , Lindeman Neal I. , Ligon Azra H. , Chiocca E. Antonio , Reardon David A. , Wen Patrick Y. , Meredith David , Santagata Sandro , Barnholtz-Sloan Jill S. , Ligon Keith L. , Beroukhim Rameen , Bi Wenya Linda
Published: September 2023

Molecularly-driven treatments are expanding options for patients with gliomas, driving a need for molecularly-informed prognostic information. To characterize the genomic landscape and contemporary outcomes of gliomas, we analyzed 4,400 gliomas from multi-institutional datasets and The Cancer Genome Atlas (TCGA): 2,195 glioblastoma, 1,198IDH1/2-mutant astrocytoma, 531 oligodendroglioma, 271 otherIDH1/2-wildtype glioma, and 205 pediatric-type glioma. Molecular classification updated 27.4% of gliomas from their original histopathologic diagnosis. Canonical alterations helped categorize glioma subtypes, revealing mutually exclusive alterations within tumorigenic pathways. Across each glioma subtype, non-TCGA patients had longer survival compared to TCGA patients. Several novel prognostic alterations emerged, includingNF1alteration and 21q loss in glioblastoma, andEGFRamplification and 22q loss inIDH1/2-mutant astrocytoma. Certain prognostic features varied across age, with decreasing prevalence ofIDH1/2-mutation over time whileMGMT-methylation remained steady. Our findings provide a framework for further exploration and validation of glioma prognostic indicators in clinically representative cohorts and trials.
The non–muscle actinopathy–associated mutation E334Q in cytoskeletal γ– actin perturbs interaction of actin filaments with myosin and ADF/cofilin family proteins
Authors: Greve Johannes N. , Marquardt Anja , Heiringhoff Robin , Reindl Theresia , Thiel Claudia , Donato Nataliya Di , Taft Manuel H. , Manstein Dietmar J.
Published: September 2023

Various heterozygous cytoskeletal γ–actin mutations have been shown to cause Baraitser–Winter cerebrofrontofacial syndrome, non–syndromic hearing loss, or isolated eye coloboma. Here, we report the biochemical characterization of human cytoskeletal γ–actin carrying mutation E334Q, a mutation that leads to a hitherto unspecified non–muscle actinopathy. Following expression, purification, and removal of linker and thymosin β4 tag sequences, the p.E334Q monomers show normal integration into linear and branched actin filaments. The mutation does not affect thermal stability, actin filament nucleation, elongation and turnover. Model building and normal mode analysis predict significant differences in the interaction of p.E334Q–filaments with myosin motors and members of the ADF/cofilin family of actin–binding proteins. Assays probing the interactions of p.E334Q–filaments with human class 2 and class 5 myosin motor constructs show significant reductions in sliding velocity and actin–affinity. E334Q differentially affects cofilin-mediated actin dynamics by increasing the rate of cofilin-mediatedde novonucleation of actin filaments and decreasing the efficiency of cofilin-mediated filament severing. Thus, it is likely that p.E334Q-mediated changes in myosin motor activity, as well as filament turnover contribute to the observed disease phenotype.
PI-(3,5)P2-mediated oligomerization of the endosomal sodium/proton exchanger NHE9
Authors: Kokane Surabhi , Meier Pascal F. , Gulati Ashutosh , Matsuoka Rei , Pipatpolkai Tanadet , Albano Giuseppe , Delemotte Lucie , Fuster Daniel , Drew David
Published: September 2023

Na+/H+exchangers are found in all cells to regulate intracellular pH, sodium levels and cell volume. Na+/H+exchangers are physiological homodimers that operate by an elevator alternating-access mechanism. While the structure of the core ion translocation domain is fairly conserved, the scaffold domain and oligomerization show larger structural variation. The Na+/H+exchanger NhaA fromE. colihas a weak oligomerization interface mediated by a β-hairpin domain and homodimerization was shown to be dependent of the lipid cardiolipin. Organellar Na+/H+exchangers NHE6, NHE7 and NHE9 are likewise predicted to contain β-hairpin domains and a recent analysis ofhorseNHE9 indicated that the lipid PIP2binds at the dimerization interface. Despite predicted lipid-mediated oligomerization, their structural validation has been lacking. Here, we report cryo-EM structures ofE. coliNhaA andhorseNHE9 with the coordination of cardiolipin and PI(3,5)P2binding at the dimer interface, respectively. Cell based assays confirms that NHE9 is inactive at the plasma membrane and thermal-shift assays, solid-supported membrane (SSM) electrophysiology and MD simulations, corroborates that NHE9 specifically binds the endosomal PI(3,5)P2lipid, which stabilizes the homodimer and enhances activity. Taken together, we propose specific lipids regulate Na+/H+exchange activity by stabilizing oligomerization and stimulating Na+binding under lipid-specific cues.
Friction forge riveting of AA7075-T6 sheets with large diameter 2117-T3 rivets
Authors: Soylak Mustafa , Erturun Veysel
Published: September 2023

Purpose

The purpose of this paper is to examine the effect of changing some riveting parameters on the riveting quality of a riveted aircraft structure. In this study, riveting was performed by applying friction under pressure.

Design/methodology/approach

During this friction riveting process, a feed of 3 mm/min was applied in the axial direction. Rotation speed values of 2,000, 2,200 and 2,400 rpm were selected. A 3-axis die milling machine was used to achieve the required positioning, pressing force and friction effect. 1.27 mm-thick Al 7075-T6 sheets and 2117-T3 forged rivets were used. The feed rate was applied at 1 mm/min in both tensile shear and cross-tensile tests.

Findings

The feasibility of friction riveting in 2117-T3 rivets was examined, it was shown that it could be done, and the most suitable rotation value for this process was determined.

Originality/value

Clamping force is one of the most important parameters for riveting quality. This study will contribute to a better understanding of the friction-forging riveting process along with the effects of riveting parameters. At the same time, it will lead to more research and expand the application of friction forging riveting to more structural connections.
Eddy current losses in power voltage transformer open-type cores
Authors: Frljić Stjepan , Trkulja Bojan , Drandić Ana
Published: September 2023

Purpose

The purpose of this paper is to present a methodology for calculating eddy current losses in the core of a single-phase power voltage transformer, which, unlike a standard power transformer, has an open-type core (I-type core). In those apparatus, reduction of core losses is achieved by using a multipart open-type core that is created by merging a larger number of leaner cores.

Design/methodology/approach

3D FEM approach for calculation of eddy current losses in open-type cores based on a weak AλA formulation is presented. Method in which redundant degrees of freedom are eliminated is shown. This enables faster convergence of the simulation. The results are benchmarked using simulations with standard AVA formulation.

Findings

Results using weak AλA formulation with elimination of redundant degrees of freedom are in agreement with both simulation using only weak AλA formulation and with simulation based on AVA formulation.

Research limitations/implications

The presented methodology is valid in linear cases, whereas the nonlinear case will be part of future work.

Practical implications

Presented procedure can be used for the optimization when designing the open-type core of apparatus like power voltage transformers.

Originality/value

The presented method is specifically adapted for calculating eddy currents in the open-type core. The method is based on a weak formulation for the magnetic vector potential A and the current vector potential λ, incorporating numerical homogenization and a straightforward elimination of redundant degrees of freedom, resulting in faster convergence of the simulation.
The relation between intellectual capital and digital transformation: a bibliometric analysis
Authors: Yilmaz Ayse Asli , Tuzlukaya Sule Erdem
Published: September 2023

Purpose

The purpose of this study is to depict the value added by digital transformation to intellectual capital (IC) by virtue of the studies reached by the literature review on different databases are examined.

Design/methodology/approach

Journal of Intellectual Capital, which has the highest number of records from the resources included in the “Web of Science” content and covering the title of “intellectual capital” has been selected in this study. Research using bibliometric analysis has been conducted and it has been determined that the terms “digital transformation” and “intellectual capital” should be searched for simultaneously in each and every article published in the journal between the years 1975 and 2022.

Findings

A bibliometric analysis and citation mapping process are carried out considering all dimensions to reach the results and interpretation of findings. VOSviewer is used to visualize the bibliometric networks of results and findings in the form of scientific mapping, as well as to visualize the co-authorship analysis of keywords, co-authorship analysis and citation networks.

Research limitations/implications

Bibliometric analysis is a method that can be used to evaluate the performance of a single journal. However, it is important to note that bibliometric analysis has some limitations when it comes to assessing the validity of a single journal. This circumstance is elaborately described as a limitation of this study. Bibliometric analysis is a method that can be used to evaluate the performance of a single journal. However, it is important to note that bibliometric analysis has some limitations when it comes to assessing the validity of a single journal. One limitation is that bibliometric analysis is based on quantitative metrics, such as citation counts, which do not take into account the quality of the research. Therefore, bibliometric analysis alone may not provide a complete picture of the validity of a single journal. In addition, bibliometric analysis is based on the number of times a paper is cited, which can be influenced by factors such as the prestige of the journal, the field of research and the time since the publication. In conclusion, bibliometric analysis can be used to evaluate the performance of a single journal, but it is important to consider its limitations.

Originality/value

This study identified contributions, gaps and limits based on the results of a bibliometric analysis. Italy is the most influential country and the issue is structured around four clusters: IC; digital transformation; human capital; and knowledge management. As previously unexplored issues are addressed in an innovative manner, it is acceptable to underline the paper’s originality.
Causes of disputes in the construction industry – a systematic literature review
Authors: Silva Pramod Malaka , Domingo Niluka , Ameer Ali Noushad Ali Naseem
Published: September 2023

Purpose

The construction industry is complex, human-intensive and driven by monetary values. Hence, disputes are widespread. Initial conflicts among parties may develop into a disastrous dispute that costs the project success and good relationships and affects stakeholders' expectations. There has been a focus on causes of construction-related disputes, and studies over the past three decades have attempted to identify a more comprehensive list of reasons for disputes. Some of these studies' limitations were geographical, project delivery methods and project types. The purpose of this study is to identify the most recent and conclusive list of causes of disputes based on current literature by undertaking a systematic literature review (SLR).

Design/methodology/approach

Considering the large number of studies that focused on causes of disputes, this study aims to develop a comprehensive list of causes, using a SLR, as it ensures that all previous articles in multiple databases are reviewed to produce a comprehensive outcome. A six-stage SLR was followed from background study to analysis and reporting.

Findings

Not surprisingly, the number of publications has increased over time, most from the Middle East region. The interconnected nature of the causes was widely emphasised. The SLR has produced eight common core causes of disputes. They are: poor contractual arrangements, employer-initiated scope changes, unforeseen site changes, poor contract understanding and administration, contractor’s quality of works, the inability of the contractor to achieve time targets, non- or delayed payments and poor quality of design. The majority of previous authors realised that disputes could be avoided by parties’ involvement during the early stages, avoiding being opportunistic and acting collaboratively.

Originality/value

Even though numerous studies have been carried out to identify the causes of disputes in the construction industry, none did a SLR. This study aggregates all the previous studies that focused on construction-related disputes systematically. Categorising causes based on the party primarily responsible help various stakeholders by providing a distinct list of factors to avoid that contribute to disputes.
Reaching out to the bottom of the pyramid to achieve financial inclusion
Authors: Shankar Amit
Published: September 2023

Purpose

This study aims to explore the factors influencing the bottom of the pyramid (BOP) consumers’ adoption and usage intention towards mobile payment (m-payment) to achieve financial inclusion and sustainable development goals.

Design/methodology/approach

A qualitative research design is used to explore the enablers and inhibitors that influence BOP consumers’ m-payment adoption and usage intention. To collect the qualitative responses, semi-structured in-depth interviews with BOP respondents were conducted. The thematic analysis using the text mining technique will be used to analyse qualitative data for exploring the predominant factors affecting m-payment adoption intention and usage.

Findings

The results suggested awareness, social influences and self-efficacy as crucial enablers and privacy and security risks and vulnerability concerns as crucial inhibitors towards m-payment adoption and usage.

Originality/value

As a novel contribution to the BOP, financial inclusion, sustainable development goals and m-payment literature, this study unfolds several unknown perceived benefits and perceived sacrifices that influence the BOP consumers’ m-payment adoption intention and usage. The study’s findings help the government and banks formulate and implement strategies to achieve financial inclusion among BOP consumers.