bluuebunny/crossref_metadata_2025_split huggingface dataset:
Donor’s age influences outcome in haploidentical hematopoietic stem cell transplantation with post-transplant cyclophosphamide - a single center experience
Authors: Zielińska Patrycja , Wieczorkiewicz-Kabut Agata , Białas Krzysztof , Koclęga Anna , Gruenpeter Karolina , Kopińska Anna , Woźniczka Krzysztof , Noster Izabela , Gromek Tomasz , Czyż Jarosław , Grosicki Sebastian , Wierzbowska Agnieszka , Krzanowski Jacek , Butrym Aleksandra , Helbig Grzegorz 
Published: June 2024

AbstractHaploidentical stem cell transplantation (haplo-SCT) using post-transplantation cyclophosphamide (post-Cy) is considered a reasonable therapeutic option for patients who lack matched donor or who urgently need transplant procedure due to high risk disease. We analyzed the results of haplo-SCT performed in years 2018–2023. Eighty one patients (46 males) at median age of 52 years underwent haplo-SCT using peripheral blood as a stem cell source in most cases. Indications included hematological malignancies (acute leukemias in 88% of cases). In 25 cases (31%) transplantation was performed in relapsed/refractory disease. Majority of patients (61%) presented with very high and high disease risk index (DRI). Conditioning regimens were as follows: nonmyeloablative − 46 cases (57%), myeloablative – in 18 (22%) and reduced intensity – 17(20%). 90% of patients engrafted. All patients received unified immunosuppressive treatment (post-Cy/TAC/MMF). Median follow-up time was 12 months The cumulative incidence of acute and chronic GVHD was 37.5% and 37.6%, respectively. Estimated 2-year overall survival (OS) was 43.1% and donor’s age was the only factor influencing survival. The 2-year progression-free survival (PFS) was 42.5%, whereas relapse incidence (RI) − 35%. The cumulative incidence of non-relapse mortality (NRM) was 44% and was mostly due to infections. Haplo-SCT is a feasible treatment option for hematological patients. Younger donor improves post-transplant survival. Strategies to reduce infection-related mortality and relapse rate remain a challenge.
Evaluation of the effect of modafinil on the pharmacokinetics of encorafenib and binimetinib in patients with BRAF V600-mutant advanced solid tumors
Authors: Piscitelli Joseph , Reddy Micaela B. , Wollenberg Lance , Del Frari Laurence , Gong Jason , Matschke Kyle , Williams Jason H. 
Published: June 2024

Abstract
Background
A clinical drug-drug interaction (DDI) study was designed to evaluate the effect of multiple doses of modafinil, a moderate CYP3A4 inducer at a 400 mg QD dose, on the multiple oral dose pharmacokinetics (PK) of encorafenib and its metabolite, LHY746 and binimetinib and its metabolite, AR00426032.

Methods
This study was conducted in patients with BRAF V600-mutant advanced solid tumors. Treatment of 400 mg QD modafinil was given on Day 15 through Day 21. Encorafenib 450 mg QD and binimetinib 45 mg BID were administered starting on Day 1. PK sampling was conducted from 0 to 8 h on Day 14 and Day 21. Exposure parameters were calculated for each patient by noncompartmental analysis and geometric least-squares mean ratio. Corresponding 90% confidence intervals were calculated to estimate the magnitude of effects.

Results
Among 11 PK evaluable patients, encorafenib Cmax and AUClast were decreased in presence of steady-state modafinil by 20.2% and 23.8%, respectively. LHY746 exposures were not substantially changed in the presence of steady-state modafinil.

Conclusion
The results from this clinical study indicate modafinil 400 mg QD had a weak effect on encorafenib PK. Based on these results, encorafenib can be coadministered with a moderate CYP3A4 inducer without dosing adjustment.

Clinical trial registration
ClinicalTrials.gov NCT03864042, registered 6 March 2019.
Population pharmacokinetics of TLD-1, a novel liposomal doxorubicin, in a phase I trial
Authors: Mc Laughlin Anna M. , Hess Dagmar , Michelet Robin , Colombo Ilaria , Haefliger Simon , Bastian Sara , Rabaglio Manuela , Schwitter Michael , Fischer Stefanie , Eckhardt Katrin , Hayoz Stefanie , Kopp Christoph , Klose Marian , Sessa Cristiana , Stathis Anastasios , Halbherr Stefan , Huisinga Wilhelm , Joerger Markus , Kloft Charlotte 
Published: June 2024

Abstract
Study objectives
TLD-1 is a novel pegylated liposomal doxorubicin (PLD) formulation aiming to optimise the PLD efficacy-toxicity ratio. We aimed to characterise TLD-1’s population pharmacokinetics using non-compartmental analysis and nonlinear mixed-effects modelling.

Methods
The PK of TLD-1 was analysed by performing a non-compartmental analysis of longitudinal doxorubicin plasma concentration measurements obtained from a clinical trial in 30 patients with advanced solid tumours across a 4.5-fold dose range. Furthermore, a joint parent-metabolite PK model of doxorubicinentrapped, doxorubicinfree, and metabolite doxorubicinol was developed. Interindividual and interoccasion variability around the typical PK parameters and potential covariates to explain parts of this variability were explored.

Results
Medians $$\pm$$
±
standard deviations of dose-normalised doxorubicinentrapped+free Cmax and AUC0−∞ were 0.342 $$\pm$$
±
0.134 mg/L and 40.1 $$\pm$$
±
18.9 mg·h/L, respectively. The median half-life (95 h) was 23.5 h longer than the half-life of currently marketed PLD. The novel joint parent-metabolite model comprised a one-compartment model with linear release (doxorubicinentrapped), a two-compartment model with linear elimination (doxorubicinfree), and a one-compartment model with linear elimination for doxorubicinol. Body surface area on the volumes of distribution for free doxorubicin was the only significant covariate.

Conclusion
The population PK of TLD-1, including its release and main metabolite, were successfully characterised using non-compartmental and compartmental analyses. Based on its long half-life, TLD-1 presents a promising candidate for further clinical development. The PK characteristics form the basis to investigate TLD-1 exposure-response (i.e., clinical efficacy) and exposure-toxicity relationships in the future. Once such relationships have been established, the developed population PK model can be further used in model-informed precision dosing strategies.

Clinical trial registration
ClinicalTrials.gov–NCT03387917–January 2, 2018
Well-Posedness and Regularity of Solutions to Neural Field Problems with Dendritic Processing
Authors: Avitabile Daniele , Chemetov Nikolai V. , Lima P. M. 
Published: June 2024

AbstractWe study solutions to a recently proposed neural field model in which dendrites are modelled as a continuum of vertical fibres stemming from a somatic layer. Since voltage propagates along the dendritic direction via a cable equation with nonlocal sources, the model features an anisotropic diffusion operator, as well as an integral term for synaptic coupling. The corresponding Cauchy problem is thus markedly different from classical neural field equations. We prove that the weak formulation of the problem admits a unique solution, with embedding estimates similar to the ones of nonlinear local reaction–diffusion equations. Our analysis relies on perturbing weak solutions to the diffusion-less problem, that is, a standard neural field, for which weak problems have not been studied to date. We find rigorous asymptotic estimates for the problem with and without diffusion, and prove that the solutions of the two models stay close, in a suitable norm, on finite time intervals. We provide numerical evidence of our perturbative results.
Intralesional combined digoxin and furosemide versus intralesional 5-flurouracil for the treatment of recalcitrant plantar warts: a prospective, randomized study
Authors: khattab Fathia , Essam Reham , Elhadidy Reham F. , Anis Nourhan 
Published: June 2024

AbstractThere are many therapeutic modalities for plantar warts, however treating it remains challenging. Intralesional injection of 5-fluorouarcil and combined digoxin and furosemide were observed to be effective and safe, however no comparison study between them was done. Our study was conducted to evaluate the efficacy of both therapies in the treatment of plantar warts. 90 adult patients with multiple recalcitrant plantar warts were included in our study. They were randomly allocated to one of three groups; combined digoxin and furosemide, 5-fluorouarcil, or normal saline group. Fortnightly injections were done into all studied warts till complete clearance or up to 5 sessions. Warts were evaluated clinically and dermoscopically. Clinical response was reported in 24 patients (80%) of the combined digoxin and furosemide group with 40% complete response and in 24 patients (80%) of the 5-fluorouarcil group with 33.3% complete response. No statistically significant difference was observed between the two groups concerning efficacy and safety. Intralesional injection of 5-fluorouarcil and combined digoxin and furosemide are nearly equivalent in efficacy and safety for plantar wart treatment. Dermoscopy helps to take the truthful judgment about complete clearance of warts.
Effectiveness of fractional erbium–YAG laser, microneedling, platelet-rich plasma in localized stable vitiligo patients: randomized clinical trial
Authors: Abdel-Hamid Soheir , Ibrahim Hassan M. , Hameed Aya M. , Hegazy Eisa M. 
Published: June 2024

AbstractVitiligo is considered an autoimmune disease, and its treatment is challenging. We assessed and compared the effect of fractional erbium:yttrium–aluminum–garnet (Er:YAG) laser-assisted delivery of platelet-rich plasma versus microneedling (Mn) with platelet-rich plasma (PRP) in enhancing skin repigmentation in localized stable vitiligo patients. In total, 40 patients with localized stable vitiligo were selected in a random manner into two similar groups (20 each). Group (A) was subjected to fractional Er:YAG laser combined with platelet-rich plasma and Group (B) was subjected to microneedling combined with platelet-rich plasma. The procedure was repeated every 2 weeks for up to 6 months. Each individual was assessed clinically utilizing Vitiligo Area Scoring Index (VASI). Fractional Er:YAG + PRP group achieved better pigmentation100% (excellent 30%, very good 15%, good 30% and satisfactory 25%) which is comparable to Mn + PRP where 80% of cases demonstrate repigmentation (20% very good, 10% good and 50% mild). When comparing the VASI scores for both groups after therapy to the baseline VASI, there was a statistically significant decrease [p = 0.001 for group(A) and 0.003 for group(B)]. Regarding the treatment side effects, there was significantly (p = 0.048) side effects among cases treated with microneedling group(B) (25%) than those fractional Er:Yag laser therapy group(A) (5%). Both forms of therapy demonstrated induction of repigmentation of vitiligo, but fractional Er:YAG laser efficacy is greater when combined with platelet-rich plasma.Clinical trials.gov identifier: NCT05511493.
Prevention of peritoneal adhesions after gynecological surgery: a systematic review
Authors: Schaefer Sebastian D. , Alkatout Ibrahim , Dornhoefer Nadja , Herrmann Joerg , Klapdor Ruediger , Meinhold-Heerlein Ivo , Meszaros Jozsef , Mustea Alexander , Oppelt Peter , Wallwiener Markus , Kraemer Bernhard 
Published: June 2024

Abstract
Importance
The formation of adhesions after gynecological surgery not only has detrimental impacts on those affected, including pain, obstruction, and infertility, but also imposes a high economic burden on healthcare systems worldwide.

Objective
The aim of this review was to evaluate the adhesion prevention potential of all currently available adhesion barriers for gynecological surgery.

Evidence acquisition
We systematically searched MEDLINE and CENTRAL databases for randomized controlled trials (RCTs) on the use of adhesion barriers as compared with peritoneal irrigation or no treatment in gynecological surgery. Only RCTs with second-look surgery to evaluate adhesions in the pelvic/abdominal (but not intrauterine) cavity were included.

Results
We included 45 RCTs with a total of 4,120 patients examining a total of 10 unique types of barriers in second-look gynecological surgery. While RCTs on oxidized regenerated cellulose (significant improvement in 6 of 14 trials), polyethylene glycol with/without other agents (4/10), hyaluronic acid and hyaluronate + carboxymethylcellulose (7/10), icodextrin (1/3), dextran (0/3), fibrin-containing agents (1/2), expanded polytetrafluoroethylene (1/1), N,O-carboxymethylchitosan (0/1), and modified starch (1/1) overall showed inconsistent findings, results for expanded polytetrafluoroethylene, hyaluronic acid, and modified starch yielded the greatest improvements regarding adhesion reduction at 75%, 0–67%, and 85%, respectively.

Conclusions and relevance
Best results for adhesion prevention were reported after applying Gore-Tex Surgical Membrane, hyaluronic acid, and 4DryField®. As Gore-Tex Surgical Membrane is nonabsorbable, it is associated with a greater risk of new adhesion formation due to second-look surgery to remove the product. 4DryField® yielded the greatest improvement in adhesion score compared to all other barrier agents (85%). For better comparability, future studies should use standardized scores and put more emphasis on patient-reported outcome measures, such as pain and infertility.
Genetics of suicide ideation. A role for inflammation and neuroplasticity?
Authors: Turiaco Fabrizio , Iannuzzo Fiammetta , Bruno Antonio , Drago Antonio 
Published: June 2024

AbstractSuicide is a leading cause of death worldwide. Suicide ideation (SI) is a known risk factor for suicide behaviour (SB). The current psychobiology and genetic predisposition to SI and SB are poorly defined. Despite convincing relevance of a genetic background for SI, there is no current implementable knowledge about the genetic makeup that identifies subjects at risk for it. One of the possible reasons for the absence of a clear-cut evidence is the polygenetic nature of SI along with the very large sample sizes that are needed to observe significant genetic association result. The CATIE sample was instrumental to the analysis. SI was retrieved as measured by the Calgary test. Clinical possible covariates were identified by a nested regression model. A principal component analysis helped in defining the possible genetic stratification factors. A GWAS analysis, polygenic risk score associated with a random forest analysis and a molecular pathway analysis were undertaken to identify the genetic contribution to SI. As a result, 741 Schizophrenic individuals from the CATIE were available for the genetic analysis, including 166,325 SNPs after quality control and pruning. No GWAS significant result was found. The random forest analysis conducted by combining the polygenic risk score and several clinical variables resulted in a possibly overfitting model (OOB error rate < 1%). The molecular pathway analysis revealed several molecular pathways possibly involved in SI, of which those involved in microglia functioning were of particular interest. A medium-small sample of SKZ individuals was analyzed to shed a light on the genetic of SI. As an expected result from the underpowered sample, no GWAS positive result was retrieved, but the molecular pathway analysis indicated a possible role of microglia and neurodevelopment in SI.
A deep-learning-based model for assessment of autoimmune hepatitis from histology: AI(H)
Authors: Ercan Caner , Kordy Kattayoun , Knuuttila Anna , Zhou Xiaofei , Kumar Darshan , Koponen Ville , Mesenbrink Peter , Eppenberger-Castori Serenella , Amini Parisa , Pedrosa Marcos C. , Terracciano Luigi M. 
Published: June 2024

AbstractHistological assessment of autoimmune hepatitis (AIH) is challenging. As one of the possible results of these challenges, nonclassical features such as bile-duct injury stays understudied in AIH. We aim to develop a deep learning tool (artificial intelligence for autoimmune hepatitis [AI(H)]) that analyzes the liver biopsies and provides reproducible, quantifiable, and interpretable results directly from routine pathology slides. A total of 123 pre-treatment liver biopsies, whole-slide images with confirmed AIH diagnosis from the archives of the Institute of Pathology at University Hospital Basel, were used to train several convolutional neural network models in the Aiforia artificial intelligence (AI) platform. The performance of AI models was evaluated on independent test set slides against pathologist’s manual annotations. The AI models were 99.4%, 88.0%, 83.9%, 81.7%, and 79.2% accurate (ratios of correct predictions) for tissue detection, liver microanatomy, necroinflammation features, bile duct damage detection, and portal inflammation detection, respectively, on hematoxylin and eosin-stained slides. Additionally, the immune cells model could detect and classify different immune cells (lymphocyte, plasma cell, macrophage, eosinophil, and neutrophil) with 72.4% accuracy. On Sirius red-stained slides, the test accuracies were 99.4%, 94.0%, and 87.6% for tissue detection, liver microanatomy, and fibrosis detection, respectively. Additionally, AI(H) showed bile duct injury in 81 AIH cases (68.6%). The AI models were found to be accurate and efficient in predicting various morphological components of AIH biopsies. The computational analysis of biopsy slides provides detailed spatial and density data of immune cells in AIH landscape, which is difficult by manual counting. AI(H) can aid in improving the reproducibility of AIH biopsy assessment and bring new descriptive and quantitative aspects to AIH histology.
CRISPR/Cas9-based genome-wide screening for metastasis ability identifies FCGR1A regulating the metastatic process of ovarian cancer by targeting LSP1
Authors: Qi Yingying , Zhu Weiyan , Mo Kexin , Jiang Hui 
Published: June 2024

Abstract
Background
Metastasis is a main cause of death from ovarian cancer (OC). Identifying key markers involved in OC metastasis can aid in the effective detection of early postoperative metastasis. However, the role of FCGR1A in OC metastasis has yet to be fully established. A genome-wide CRISPR/Cas9-based screening system was used to identify regulatory factors involved in metastasis.

Methods
The expression of FCGR1A and LSP1 in ovarian cancer cell lines was examined by quantitative real-time polymerase chain reaction (qRT‒PCR). The functions of FCGR1A and LSP1 in OC cell migration, invasion and proliferation were determined using wound healing, Transwell invasion and CKK-8 assays. A transcription-activated library was used to identify the potential downstream genes of FCGR1A. FCGR1A expression was detected by immunohistochemistry and the immunity risk score (IRS) scores were calculated.

Results
FCGR1A was upregulated in OC cells compared with normal ovarian cells. Downregulation of FCGR1A inhibited metastasis, proliferation and epithelial–mesenchymal transition (EMT) progression in OC cells in vitro and intraperitoneal metastasis in vivo. Moreover, downregulation of FCGR1A was accompanied by decreased LSP1 expression. Overexpression of LSP1 partially reversed the tumor suppressive effect of FCGR1A downregulation. Higher FCGR1A expression was related to metastasis, higher grade, higher stage, and lymph node metastasis in OC. Survival analysis suggested that the group with higher FCGR1A expression had a lower tumor-free survival rate and a lower overall survival rate than did the group with low FCGR1A expression.

Conclusions
FCGR1A enhances OC metastasis by regulating LSP1, and FCGR1A is associated with poor prognosis, suggesting that FCGR1A is a potential predictive factor for detecting early postoperative metastasis.
Pharmacological treatment of cancer pain and opioid induced nausea and vomiting: online survey and comparison with current guidelines
Authors: Gaertner Jan , Boehlke Christopher , Kreye Gudrun , Fusi-Schmidhauser Tanja , Mueller Evelyn , Roch Carmen 
Published: June 2024

Abstract
Purpose
We assumed that in Palliative Care, even in common clinical situations, the choice of drugs differs substantially between physicians. Therefore, we assessed the practice of pharmaceutical treatment choices of physicians for cancer pain and opioid-induced nausea and vomiting (OINV) and the rationale for their choices.

Methods
An online survey was conducted with physicians covering the following domains: i) Cancer pain therapy: non-opioids in addition to opioids: choice of drug ii) prevention of OINV: choice of drug and mode of application. Current guidelines concerning cancer pain therapy and prevention of OINV were compared.

Results
Two-hundred-forty European physicians responded to our survey. i) Use of non-opioids in addition to opioids for the treatment of cancer pain: Only 1.3% (n = 3) of respondents never used an additional non-opioid. Others mostly used: dipyrone/metamizole (49.2%, n = 118), paracetamol/acetaminophen (34.2%, n = 82), ibuprofen / other NSAIDs (11.3%, n = 27), specific Cox2-inhibitors (2.1%, n = 5), Aspirin (0.4%, n = 1), no answer (2.9%, n = 7). ii) Antiemetics to prevent OINV: The drugs of choice were metoclopramide (58.3%, n = 140), haloperidol (26.3%, n = 63), 5-HT3 antagonists (9.6%, n = 23), antihistamines (1.3%, n = 3) and other (2.9%, n = 7); no answer (1.7%, n = 4). Most respondents prescribed the substances on-demand (59.6%, n = 143) while others (36.3%, n = 87) provided them as around the clock medication. Over both domains, most physicians answered that their choices were not based on solid evidence from randomized controlled trials (RCTs). Guidelines were inconsistent regarding if and what non-opioid to use for cancer pain and recommend anti-dopaminergic drugs for prevention or treatment of OINV.

Conclusions
Physician’s practice in palliative care for the treatment of cancer pain and OINV differed substantially. Respondents expressed the lack of high-quality evidence- based information from RCTs. We call for evidence from methodologically high-quality RCTs to be available to inform physicians about the benefits and harms of pharmacological treatments for common symptoms in palliative care.
P-move: a randomized control trial of exercise in patients with advanced pancreatic or biliary tract cancer (aPBC) receiving beyond first-line chemotherapy
Authors: De Lazzari Nico , Götte Miriam , Kasper Stefan , Meier Eileen , Schuler Martin , Pogorzelski Michael , Siveke Jens T. , Tewes Mitra 
Published: June 2024

Abstract
Purpose
Patients with advanced pancreatic and biliary tract cancer (aPBC) frequently suffer from high symptom burden. Exercise can reduce treatment side effects and improve patient-related outcomes (PROMs). However, evidence from prospective studies regarding feasibility and efficacy in advanced settings are sparse. The primary aim of this prospective, randomized-controlled study was to evaluate the feasibility and effects of exercise (ET) in patients with aPBC.

Methods
Patients with aPBC beyond first-line therapy were randomized according to the minimization procedure with stratification by gender, age, and loss of body weight in the past six months. The intervention group (IG) completed 3 training units/week for 8 weeks (1x supervised strength sessions, 2x individualized home-based sessions). Control group (CG) received recommendations on physical activity during cancer.

Results
41 patients (stage IV pancreatic or biliary tract cancer) were included no adverse events related to exercise occurred during the trial. Physical function increased significantly in IG in 5 out of 7 physical domains. Comparison of IG and CG at 8 weeks (t2) showed significant differences in favour of IG in leg press (p=0.001), bench press (p=0.011), sit-to-stand (p=0.001) and crunch (0.006). Constipation revealed a significant difference in favour of IG at t2 (p=0.033). Quality of life stabilized/increased in IG during the study period compared to a decrease in CG. Throughout/Over the 8 weeks, fatigue notably reduced in the IG (p=0.028).

Conclusion
Exercise is safe and feasible in patients with aPBC undergoing further line therapy. Significant improvements in physical functioning and increased quality of life were achieved.
German Clinical Trials Register ID: DRKS00021179; Registration date 15.05.2020