bluuebunny/crossref_metadata_2025_split huggingface dataset:
Novel Combinations of Immunotherapies or DNA Damage Repair Inhibitors in Platinum-Refractory Extensive-Stage Small Cell Lung Cancer: The Phase II BALTIC Study
Authors: Reinmuth Niels , Juan-Vidal Oscar , Kowalski Dariusz , Bryl Maciej , Kryzhanivska Anna , Vicente David , Horváth Zsolt , Gálffy Gabriella , Csánky Eszter , Pápai Székely Zsolt , Vynnychenko Ihor , Armstrong Jon , Dalvi Tapashi , Xie Mingchao , Iyer Sonia , Shrestha Yashaswi , Jiang Haiyi , Bondarenko Igor 
Published: July 2024

Abstract

Purpose:
The phase II, multiarm, signal-searching BALTIC study (NCT02937818) assessed novel treatment combinations for platinum-refractory/resistant extensive-stage small cell lung cancer (ES-SCLC).

Patients and Methods:
Patients with ES-SCLC with progressive disease during or within 90 days of completing first-line platinum-based chemotherapy received one of three regimens: durvalumab plus tremelimumab followed by durvalumab monotherapy (arm A), adavosertib plus carboplatin (arm B), or ceralasertib plus olaparib (arm C). The primary endpoint was the objective response rate. Prespecified exploratory biomarker analyses were conducted in arms A and C.

Results:
In arm A (n = 41), arm B (n = 10), and arm C (n = 21), the confirmed objective response rates were 7.3%, 0%, and 4.8%, respectively. Safety profiles in all arms were consistent with those of the individual drugs. In arm A, patients with PD-L1 expression (tumor cells or immune cells) ≥1% seemed to have a greater likelihood of achieving disease control with durvalumab plus tremelimumab than those with PD-L1 (tumor cells and immune cells) &lt;1%, and lower baseline ctDNA and reduction in the on-treatment ctDNA level were both associated with longer overall survival. Among patients treated with ceralasertib plus olaparib in arm C, specific immune response-relevant circulating chemokines and cytokines were identified as early biomarkers of survival and pharmacodynamic biomarkers.

Conclusions:
In BALTIC, all combination regimens demonstrated tolerable safety profiles, but antitumor activity was limited in refractory/resistant ES-SCLC. Among patients treated with durvalumab plus tremelimumab, an association of on-treatment reduction in ctDNA with longer overall survival suggests the potential use of ctDNA as a surrogate of treatment response, warranting further investigation.
Oral and Gut Microbiome Alterations in Oral Chronic GVHD Disease: Results from Close Assessment and Testing for Chronic GVHD (CATCH Study)
Authors: Rashidi Armin , Pidala Joseph , Hamilton Betty K. , Pavletic Steven Z. , Kim Katie , Zevin Alex , Mays Jacqueline W. , Lee Stephanie J. 
Published: July 2024

Abstract

Purpose:
Whether and how the oral microbiome and its changes in allogeneic hematopoietic cell transplantation (alloHCT) recipients may contribute to oral chronic GVHD (cGVHD) pathogenesis is unknown. In addition, although the oral and colonic microbiota are distinct in healthy adults, whether oral microbes may ectopically colonize the gut in alloHCT patients is unknown.

Experimental Design:
To address these knowledge gaps, longitudinal oral and fecal samples were collected prospectively in the multicenter Close Assessment and Testing for Chronic GVHD study (NCT04188912). Through shotgun metagenomic sequencing of the samples collected at baseline, oral cGVHD onset, first post-cGVHD onset visit, and 1-year post-HCT time points in patients with oral cGVHD (cases; N = 29) or without any cGVHD (controls; N = 51), we examined whether (i) oral and/or gut microbiomes and their longitudinal trajectories differ between cases and controls and (ii) oral and gut microbiomes overlap in alloHCT recipients, especially those developing cGVHD.

Results:
A total of 195 samples were analyzed. The onset of oral cGVHD was characterized by an expansion of Streptococcus salivarius and Veillonella parvula in the oral microbiome. High levels of oral/gut microbiota overlap were observed, particularly in patients with oral cGVHD, suggesting ectopic colonization of the gut by oral bacteria.

Conclusions:
The unusual coalescence of two distant niches in these patients may result in short- or long-term consequences for the host, a novel avenue for future research. In addition, this study suggests a contribution of the oral microbiome to oral cGVHD pathogenesis.
PIKing up and AKTing on Resistance Mutations in Osimertinib-Treated EGFR-Mutated NSCLC
Authors: Vokes Natalie I. , Le Xiuning , Yap Timothy A. 
Published: July 2024

Summary
A recent study identified high rates of PI3K–AKT pathway mutations from the FLAURA and AURA3 osimertinib trials and pre-clinically validated that these mutations decreased osimertinib sensitivity in EGFR-mutated non–small cell lung cancer. The AKT inhibitor capivasertib was found to overcome this resistance, providing an important rationale for the development of AKT inhibitors in non–small cell lung cancer.
See related article by Grazini et al., p. 4143
GRAIL1 Stabilizes Misfolded Mutant p53 through a Ubiquitin Ligase-Independent, Chaperone Regulatory Function
Authors: Ray Paramita , Jaiswal Sangeeta , Ferrer-Torres Daysha , Wang Zhuwen , Nancarrow Derek , Curtin Meghan , Martinho May San , Lacy Shannon M. , Kasturirangan Srimathi , Thomas Dafydd , Spence Jason R. , Truttmann Matthias C. , Lagisetty Kiran H. , Lawrence Theodore S. , Wang Thomas D. , Beer David G. , Ray Dipankar 
Published: July 2024

Abstract
Frequent (&gt;70%) TP53 mutations often promote its protein stabilization, driving esophageal adenocarcinoma (EAC) development linked to poor survival and therapy resistance. We previously reported that during Barrett’s esophagus progression to EAC, an isoform switch occurs in the E3 ubiquitin ligase RNF128 (aka GRAIL—gene related to anergy in lymphocytes), enriching isoform 1 (hereby GRAIL1) and stabilizing the mutant p53 protein. Consequently, GRAIL1 knockdown degrades mutant p53. But, how GRAIL1 stabilizes the mutant p53 protein remains unclear. In search for a mechanism, here, we performed biochemical and cell biology studies to identify that GRAIL has a binding domain (315-PMCKCDILKA-325) for heat shock protein 40/DNAJ. This interaction can influence DNAJ chaperone activity to modulate misfolded mutant p53 stability. As predicted, either the overexpression of a GRAIL fragment (Frag-J) encompassing the DNAJ binding domain or a cell-permeable peptide (Pep-J) encoding the above 10 amino acids can bind and inhibit DNAJ-Hsp70 co-chaperone activity, thus degrading misfolded mutant p53. Consequently, either Frag-J or Pep-J can reduce the survival of mutant p53 containing dysplastic Barrett’s esophagus and EAC cells and inhibit the growth of patient-derived organoids of dysplastic Barrett’s esophagus in 3D cultures. The misfolded mutant p53 targeting and growth inhibitory effects of Pep-J are comparable with simvastatin, a cholesterol-lowering drug that can degrade misfolded mutant p53 also via inhibiting DNAJA1, although by a distinct mechanism.
Implications: We identified a novel ubiquitin ligase-independent, chaperone-regulating domain in GRAIL and further synthesized a first-in-class novel misfolded mutant p53 degrading peptide having future translational potential.
Membrane-bound Heat Shock Protein mHsp70 Is Required for Migration and Invasion of Brain Tumors
Authors: Shevtsov Maxim , Bobkov Danila , Yudintceva Natalia , Likhomanova Ruslana , Kim Alexander , Fedorov Evegeniy , Fedorov Viacheslav , Mikhailova Natalia , Oganesyan Elena , Shabelnikov Sergey , Rozanov Oleg , Garaev Timur , Aksenov Nikolay , Shatrova Alla , Ten Artem , Nechaeva Anastasiya , Goncharova Daria , Ziganshin Rustam , Lukacheva Anastasiya , Sitovskaya Daria , Ulitin Alexey , Pitkin Emil , Samochernykh Konstantin , Shlyakhto Evgeny , Combs Stephanie E. 
Published: July 2024

Abstract

Molecular chaperones, especially 70 kDa heat shock protein, in addition to their intracellular localization in cancer cells, can be exposed on the surface of the plasma membrane. We report that the membrane-associated chaperone mHsp70 of malignant brain tumors is required for high migratory and invasive activity of cancer cells. Live-cell inverted confocal microscopy of tumor samples from adult (n = 23) and pediatric (n = 9) neurooncologic patients showed pronounced protein expression on the membrane, especially in the perifocal zone. Mass spectrometry analysis of lipid rafts isolated from tumor cells confirmed the presence of the protein in the chaperone cluster (including representatives of other families, such as Hsp70, Hsc70, Hsp105, and Hsp90), which in turn, during interactome analysis, was associated with proteins involved in cell migration (e.g., Rac1, RhoC, and myosin-9). The use of small-molecule inhibitors of HSP70 (PES and JG98) led to a substantial decrease in the invasive potential of cells isolated from a tumor sample of patients, which indicates the role of the chaperone in invasion. Moreover, the use of HSP70 inhibitors in animal models of orthotopic brain tumors significantly delayed tumor progression, which was accompanied by an increase in overall survival. Data demonstrate that chaperone inhibitors, particularly JG98, disrupt the function of mHsp70, thereby providing an opportunity to better understand the diverse functions of this protein and offer aid in the development of novel cancer therapies.

Significance:
Membrane-bound mHsp70 is required for brain tumor cell migration and invasion and therefore could be employed as a target for anticancer therapies.
Integrating anatomical and functional landmarks for interparticipant alignment of imaging data
Authors: Jeganathan Jayson , Paton Bryan , Koussis Nikitas , Breakspear Michael 
Published: July 2024

Abstract
Aligning brain maps using functional features rather than anatomical landmarks potentially improves individual identifiability and increases power in group neuroimaging studies. However, alignment based purely on functional magnetic resonance imaging (fMRI) risks omitting useful anatomical constraints. An optimized combination of anatomical and functional feature alignment could balance the advantages of each approach. We used 3T fMRI data from 80 Human Connectome Project participants during seven tasks. The effectiveness of functional and anatomical alignment methods was evaluated using interparticipant decoding accuracy. Functional alignment mapped vertices from participants to a template, aligning their fMRI responses to shared responses during movie viewing. The template was derived from the combined fMRI responses of a set of participants. We benchmarked the results against existing functional alignment methods, including the Procrustes method and ridge regression. A common practice in the field is to use the same participants for the alignment cohort and for template generation. We found that this inflates decoding accuracies by mixing anatomical and functional alignment. Based on this, we recommend that a template’s generalizability should be evaluated against held-out participants. Building on these findings, we investigated whether inter-subject alignment could be improved by integrating anatomical and functional information. We studied a modified alignment method where a single parameter interpolates between pure functional alignment and anatomical alignment. Optimizing the parameter with nested cross-validation, we found that integrating anatomical and functional information robustly reduced noise and improved alignment across a variety of alignment methods. Combining anatomical and functional information accounts for individual heterogeneity in functional topographies while incorporating anatomical constraints. The integrated alignment described here improves inter-subject decoding using functional brain maps. These findings also demonstrate that brain anatomy provides a lens into the inherent variability of individual neural landscapes.
Weaning failure due to isolated residual diaphragmatic paralysis after cervical spinal cord ischemia following aortic surgery- a case report
Authors: Overbeek Remco , Behrens Amelie , Zopfs David , Mylonas Spyridon , Dorweiler Bernhard , Dusse Fabian , Böttiger Bernd W. , Stoll Sandra Emily 
Published: July 2024

Abstract
Background
Bilateral diaphragmatic dysfunction can lead to dyspnea and recurrent respiratory failure. In rare cases, it may result from high cervical spinal cord ischemia (SCI) due to anterior spinal artery syndrome (ASAS). We present a case of a patient experiencing persistent isolated diaphragmatic paralysis after SCI at level C3/C4 following thoracic endovascular aortic repair (TEVAR) for Kommerell’s diverticulum. This is, to our knowledge, the first documented instance of a patient fully recovering from tetraplegia due to SCI while still exhibiting ongoing bilateral diaphragmatic paralysis.

Case presentation
The patient, a 67-year-old male, presented to the Vascular Surgery Department for surgical treatment of symptomatic Kommerell’s diverticulum in an aberrant right subclavian artery. After successful surgery in two stages, the patient presented with respiratory insufficiency and flaccid tetraparesis consistent with anterior spinal artery syndrome with maintained sensibility of all extremities. A computerized tomography scan (CT) revealed a high-grade origin stenosis of the left vertebral artery, which was treated by angioplasty and balloon-expandable stenting. Consecutively, the tetraparesis immediately resolved, but weaning remained unsuccessful requiring tracheostomy. Abdominal ultrasound revealed a residual bilateral diaphragmatic paralysis. A repeated magnetic resonance imaging (MRI) 14 days after vertebral artery angioplasty confirmed SCI at level C3/C4. The patient was transferred to a pulmonary clinic with weaning center for further recovery.

Conclusions
This novel case highlights the need to consider diaphragmatic paralysis due to SCI as a cause of respiratory failure in patients following aortic surgery. Diaphragmatic paralysis may remain as an isolated residual in these patients.
A combined endovascular and open repair of innominate artery bifurcation pseudoaneurysm: a case report
Authors: Xu Youyao , Zhu Tao , Chen Guobin , Wu Senyan , Li Xiaoyang 
Published: July 2024

Abstract
Background
Innominate artery aneurysms (IAAs) are rare and may result in rupture, distal arterial embolization, or local compression without timely treatment. Rupture is the most dangerous of these complications. This article reports a case of innominate artery bifurcation pseudoaneurysm.

Case presentation
The patient was a 45-year-old man who was admitted to the emergency department due to chest discomfort. The computed tomographic angiography (CTA) imaging indicated the presence of a 3.6*2.4 cm saccular aneurysm in the bifurcation of the innominate artery, involving both the right proximal subclavian and common carotid arteries. The patient’s vital signs were normal, there was equal blood pressure in the upper arms and no neurological dysfunction was observed. Gadolinium-enhanced magnetic resonance angiography indicated that the circle of Willis was intact. The treatment involved open surgery combined with endovascular therapy. The external carotid artery was first transposed to the right subclavian artery (RSA) and an 8-mm woven Dacron graft was inserted in the middle. The covered stent graft was then placed in the proximal part of the innominate artery to close the entrance of the aneurysm. Lastly, an occluder was implanted at the origin of the RSA. There were no perioperative or postoperative complications. At 1-year follow-up, no aneurysm was observed on CTA and the right vertebral artery was patent.

Conclusions
This study indicated that the combined use of endovascular therapy and open repair surgery is an effective strategy to treat innominate artery bifurcation pseudoaneurysm.
Current situation, strengths and problems in intra- and interprofessional collaboration in German nursing homes – A holistic multiple case study
Authors: Schmüdderich Kathrin , Dörner Jonas , Fahsold Anne , Palm Rebecca , Roes Martina , Holle Bernhard 
Published: July 2024

Abstract
Background
The increasing care complexity of nursing home residents living with dementia requires new care models that strengthen professional collaboration. To contribute to the sustainable implementation of new care models, it is important that they are linked to the care reality. However, little is known about intra- and interprofessional organization and provision of care in German nursing homes. Therefore, the aim of this study was to explore the current care situation, problems and strengths regarding intra- and interprofessional collaboration in the care of residents living with dementia.

Methods
We conducted a holistic multiple case study. The individual care units in which residents living with dementia are cared for were defined as cases. The context was built by the respective nursing homes and their regional affiliation to the federal state of North Rhine-Westphalia. We used qualitative face-to-face interviews, documents and context questionnaires for data collection. The different sources of evidence served to capture complementary perspectives and to validate the findings. First, the collected qualitative data were analyzed using deductive-inductive content analysis. Second, similarities and differences between the cases were identified to elaborate case-specific and cross-case patterns and themes. The reporting followed the EQUATOR reporting guideline for organizational case studies.

Results
We included four care units comprising 21 professionals (nurses, physicians, social worker, physiotherapist, pharmacist) and 14 relatives of residents living with dementia. The analysis revealed four categories to describe current intra- and interprofessional collaboration in all cases: actors and their roles, service delivery, coordination and governance, and communication channel. Moreover, we identified three categories that relate to the strengths and problems of intra- and interprofessional collaboration in all cases: role understanding, teamwork, and communication and exchange. Although we examined similar care units, we found differences in the realization of professional collaboration and resulting problems and strengths that are connected to the organizational contexts and strategies used.

Conclusions
Even though professional collaboration follows given patterns; these patterns do differ context-specifically and are perceived as problematic and fragmentary. Therefore, the identified differences and problems in collaboration need to be addressed in future research to develop and successfully implement tailored innovative care models.
Increased level of TXNIP and nuclear translocation of TXN is associated with end stage renal disease and development of multiplex renal tumours
Authors: Beothe Tamas , Docs Janos , Kovacs Gyula , Peterfi Lehel 
Published: July 2024

Abstract
Background
End-stage and acquired cystic renal disease (ESRD/ACRD) kidneys are characterized by inflammatory remodelling and multiplex renal cell carcinomas (RCC). Eosinophilic vacuolated tumour (EVT) occurs exclusively in ACRD. The aim of this study was to identify the involvement of thioredoxin-interacting protein (TXNIP) and thioredoxin (TXN) in ESRD/ACRD pathology.

Methods
Expression of TXNIP and TXN was examined in histological slides of 6 ESRD and 6 ACRD kidneys, precursor lesions and associated tumours as well as of RCCs from the general population by immunohistochemistry.

Results
Strong TXNIP expression was seen in epithelial cells, myo-fibroblasts and endothelial cells and weak TXN expression in ESRD/ACRD kidneys and tumours. In ACRD specific EVT and its precursors TXN were translocated into nuclei.

Conclusion
The impaired TXNIP/TXN redox homeostasis might be associated with development of multiplex cancer especially of EVT in ESRD/ACRD kidney.
Knowledge, attitude, and perception towards COVID-19 vaccinations among the adults in Rwanda: a cross-sectional study
Authors: Gabriel Abakundana Nsenga Ariston , Wang Xiao-Yang , Jamil Laila , Shimbre Mulugeta Shegaze , Bikorimana Gerard , Zhao Lin , Cao Wu-Chun 
Published: July 2024

Abstract
Background
Multiple vaccinations have received approval for the prevention of the coronavirus illness. Nevertheless, the sluggish vaccination rate is mostly attributed to the general population’s limited understanding and unwillingness to accept the use of vaccinations. Thus, it is important to investigate the Rwandan population’s knowledge, attitudes, and perceptions toward COVID-19 vaccines.

Methods
A cross-sectional survey was conducted among 370 participants from 11th to 17th February 2023. Demographic information was gathered, and knowledge, attitudes, and perceptions of COVID-19 vaccinations were assessed. A binary logistic regression analysis was undertaken to determine the parameters that determine the perception of COVID-19 vaccinations.

Results
This study included 370 participants. Among them, 85% had good knowledge about COVID-19 vaccines, and 84% had a positive attitude towards them. Additionally, the study had a diverse group, with half of the participants being female and nearly half falling between the ages of 30 and 39. Several key findings emerged through logistic regression analysis. Those aged 30–39 had 1.39 times higher odds of positive perception than 18–28 (OR = 1.39, 95% CI = 1.08–3.24). Participants with a university education were twice as likely to have a positive perception compared to those without an education level (OR = 2.43, 95% CI = 1.30–6.20). Additionally, single individuals were three times more likely to have a positive perception than their married counterparts (OR = 3.39, 95% CI = 1.28–9.09). Vaccinated individuals had twice the odds of positive perception than non-vaccinated individuals (OR = 2.89, 95% CI = 1.01–8.89). Those receiving information from government health institutions were three times more likely to have a positive perception than those who received the information from friends (OR = 3.19, 95% CI = 1.02–12.7). Moreover, employed participants were four times more likely to have a positive perception non-employed individuals (OR = 4.21, 95% CI = 1.48–13.6). Besides, gender and COVID-19 diagnosis did not significantly correlate with positive COVID-19 vaccine perception.

Conclusion
The results indicate that the general public in Rwanda has good knowledge, positive attitudes, and a positive perception toward the COVID-19 vaccination, however, some of the participants had some misconceptions towards COVID-19. The findings of this study will be valuable for policymakers and healthcare authorities working to improve vaccination rates.