bluuebunny/crossref_metadata_2025_split huggingface dataset:
Psilocybin‐assisted group therapy in patients with cancer diagnosed with a major depressive disorder
Authors: Agrawal Manish , Richards William , Beaussant Yvan , Shnayder Sarah , Ameli Rezvan , Roddy Kimberly , Stevens Norma , Richards Brian , Schor Nick , Honstein Heather , Jenkins Betsy , Bates Mark , Thambi Paul 
Published: December 2023

AbstractBackgroundDepression is common in patients with cancer and is associated with lower treatment adherence and reduced quality of life. Antidepressants and psychotherapy have limited success in improving depression among patients with cancer. This study explored the safety, feasibility, and efficacy of psilocybin‐assisted therapy in patients with cancer and major depressive disorder.MethodsThis phase 2, open‐label trial enrolled patients with curable and noncurable cancer and major depressive disorder at a single community oncology practice site. A single 25‐mg dose of psilocybin was administered simultaneously to cohorts of three to four participants with individual (4.25 hours in 1:1 therapist‐to‐patient ratio) and group therapeutic support (3.75 hours) before, during, and after psilocybin administration. Outcomes included depression severity, anxiety, pain, demoralization, and disability.ResultsThirty participants completed the study. No psilocybin‐related serious adverse events occurred; treatment‐related adverse events (e.g., nausea, headache) were generally mild and expected. There were no laboratory or electrocardiogram abnormalities. No suicidality was reported. Efficacy was suggested with a robust reduction in depression severity scores from baseline to posttreatment of 19.1 points (95% CI, 22.3 to –16.0; p < .0001) by week 8. Eighty percent of participants demonstrated a sustained response to psilocybin treatment; 50% showed full remission of depressive symptoms at week 1, which was sustained for 8 weeks.ConclusionsPsilocybin‐assisted therapy in group cohort administration was safe and feasible in patients with cancer and depression. Efficacy was suggested based on clinically meaningful reductions in depressive symptoms. The novel, group‐oriented format, compact delivery time, community cancer center setting, and one‐to‐one therapist‐to‐patient ratio could also add to therapeutic gains and efficiency of administration.Trial RegistrationNCT04593563.Plain Language Summary

Depression is common in patients with cancer and associated with lower treatment adherence, reduced quality of life, and limited response to antidepressants and psychotherapy.
We conducted a phase 2 trial to study a single dose of psilocybin administered in a group therapy setting with one‐to‐one therapist‐to‐participant psychological support to patients with curable and noncurable cancer and major depressive disorder.
Findings of the study showed safety (no treatment‐related serious adverse events or suicidality) with psilocybin and suggested efficacy, with a significant reduction in depression severity scores from baseline to posttreatment. Further investigation is warranted.
Safety, Tolerability, and Pharmacokinetics of a Novel Oral Phosphodiesterase 4 Inhibitor, ME3183: First‐in‐Human Phase 1 Study
Authors: Kato Seiji , Cho Naoki , Koresawa Tomokazu , Otake Kazunari , Kano Akiko 
Published: December 2023

AbstractA novel, oral phosphodiesterase 4 (PDE4) inhibitor, ME3183, is under development for the treatment of psoriasis, atopic dermatitis, and other inflammatory diseases. To evaluate its safety, tolerability, and pharmacokinetics, double‐blind, placebo‐controlled, single ascending dose (SAD), and multiple ascending dose (MAD) phase 1 studies were conducted in 126 healthy adults. The food effect was evaluated in a randomized, open‐label, crossover manner (n = 5). ME3183 was safe and tolerable up to 25 mg in the SAD part and up to 10 mg twice daily in the MAD part. Frequently observed treatment‐emergent adverse events included diarrhea and headache, as commonly reported for approved PDE4 inhibitors, providing no novel safety concerns. Pharmacokinetic analysis showed dose‐dependent increases in Cmax and AUC, with later tmax and longer t1/2 than apremilast, an approved PDE4 inhibitor. The food effect study showed slightly decreased systemic exposure. In the MAD part, plasma exposure levels of ME3183 were higher even at the minimal dose (2.5 mg twice daily) than the estimated therapeutically effective level. These results show the safe profile of ME3183 and support further studies to confirm the safety and efficacy of the drug in patients with psoriasis and other inflammatory diseases.
Assessment of the CYP3A4 Induction Potential by Carbamazepine: Insights from Two Clinical DDI Studies and PBPK Modeling
Authors: Kanefendt Friederike , Dallmann André , Chen Huijun , Francke Klaus , Liu Tianxing , Brase Christine , Frechen Sebastian , Schultze‐Mosgau Marcus‐Hillert 
Published: December 2023

In the past, rifampicin was well‐established as strong index CYP3A inducer in clinical drug–drug interaction (DDI) studies. However, due to identified potentially genotoxic nitrosamine impurities, it should not any longer be used in healthy volunteer studies. Available clinical data suggest carbamazepine as an alternative to rifampicin as strong index CYP3A4 inducer in clinical DDI studies. Further, physiologically‐based pharmacokinetic (PBPK) modeling is a tool with increasing importance to support the DDI risk assessment of drugs during drug development. CYP3A4 induction properties and the safety profile of carbamazepine were investigated in two open‐label, fixed sequence, crossover clinical pharmacology studies in healthy volunteers using midazolam as a sensitive index CYP3A4 substrate. Carbamazepine was up‐titrated from 100 mg twice daily (b.i.d.) to 200 mg b.i.d., and to a final dose of 300 mg b.i.d. for 10 consecutive days. Mean area under plasma concentration‐time curve from zero to infinity (AUC(0‐∞)) of midazolam consistently decreased by 71.8% (ratio: 0.282, 90% confidence interval (CI): 0.235–0.340) and 67.7% (ratio: 0.323, 90% CI: 0.256–0.407) in study 1 and study 2, respectively. The effect was adequately described by an internally developed PBPK model for carbamazepine which has been made freely available to the scientific community. Further, carbamazepine was safe and well‐tolerated in the investigated dosing regimen in healthy participants. The results demonstrated that the presented design is appropriate for the use of carbamazepine as alternative inducer to rifampicin in DDI studies acknowledging its CYP3A4 inductive potency and safety profile.
Catalytic Domino Three‐Component Synthesis of Functionalized Heterocycles from Carbon Dioxide
Authors: Shi Wangyu , Qiao Chang , Benet‐Buchholz Jordi , Kleij Arjan W. 
Published: December 2023

AbstractA catalytic domino, three‐component reaction has been developed for the transformation of carbon dioxide into functionalized six‐membered cyclic carbonates. The catalytic process combines an initial carboxylative cyclization of β‐epoxy alcohols followed by an oxa‐Michael reaction affording an unparalleled scope of heterocyclic structures. The wide range of functional groups, including free‐alcohols, empowers the access to a range of products including C11‐oxo‐based bicyclic heterocycles. The versatility of these functionalized carbonates is further complemented by a series of synthetic diversifications. Control experiments are consistent with the first step of this domino process being promoted by a binary Lewis acid/base catalyst, while the second stage only requires catalytic base.
Exploratory correlation of the human structural connectome with non‐MRI variables in Alzheimer's disease
Authors: Aganj Iman , Mora Jocelyn , Frau‐Pascual Aina , Fischl Bruce ,   for the Alzheimer's Disease Neuroimaging Initiative
Published: December 2023

AbstractIntroductionDiscovery of the associations between brain structural connectivity and clinical and demographic variables can help to better understand the vulnerability and resilience of the brain architecture to neurodegenerative diseases and to discover biomarkers.MethodsWe used four diffusion‐MRI databases, three related to Alzheimer's disease (AD), to exploratorily correlate structural connections between 85 brain regions with non‐MRI variables, while stringently correcting the significance values for multiple testing and ruling out spurious correlations via careful visual inspection. We repeated the analysis with brain connectivity augmented with multi‐synaptic neural pathways.ResultsWe found 85 and 101 significant relationships with direct and augmented connectivity, respectively, which were generally stronger for the latter. Age was consistently linked to decreased connectivity, and healthier clinical scores were generally linked to increased connectivity.DiscussionOur findings help to elucidate which structural brain networks are affected in AD and aging and highlight the importance of including indirect connections.
Facies distribution and depositional cycles in lacustrine and palustrine carbonates: The Lutetian–Aquitanian record in the Paris Basin
Authors: Moreau Kévin , Andrieu Simon , Briais Justine , Brigaud Benjamin , Ader Magali 
Published: December 2023

AbstractThe difficulty of correlating continental deposits hinders predicting lacustrine and palustrine carbonate facies variations in time and space. This study aims to understand better the factors governing these facies heterogeneities by measuring carbonate isotopes and conducting facies, petrographic and sequence stratigraphic analyses of the Lutetian–Aquitanian deposits of the Paris Basin, that record the transition from marine to lacustrine environments. Large‐scale correlations enabled the definition of two lacustrine–palustrine carbonate facies models. (1) The coastal lacustrine system (Bartonian to Rupelian), consists of fine‐grained brackish carbonate exhibiting episodic marine inputs during short‐term relative sea‐level maxima and evaporite sedimentation during relative sea‐level minima. Lacustrine sediments differ notably from marine ones with more negative δ13C and δ18O compositions that co‐vary and a biota adapted to low salinity conditions. In the associated palustrine environment, depositional sequences evolve upwards from micritic lacustrine deposits to nodular and then laminar calcretes. Microbial‐coated grains and rhizoliths indicate biological processes during repeated subaerial exposure phases in sub‐tropical to arid climates. (2) The inland lacustrine system (Rupelian and Aquitanian) was disconnected from the marine domain and showed evidence of microbial activity with microbial crusts and oncoidal rudstones. Facies rich in micritic intraclasts composed of palustrine and lacustrine facies indicate the reworking of already lithified sediments along the margins. In the palustrine domain, the calcrete facies are less abundant than breccias formed in‐situ by desiccation, limestones with root traces, or organic‐rich wackestones and marls. This system reflects a more temperate climate with more developed microbial structures and less exposed carbonates than the coastal lacustrine system. The southward migration of the depocentre and the transition from marine environments to (1) coastal and then (2) inland systems are controlled by uplift phases induced by Pyrenean and Alpine orogenesis. Third‐order relative sea‐level variations appear to control only short‐term cycles in coastal systems.
Synthesis of 2,5‐Disubstituted Pyridines using the Gold(I)‐Catalyzed Cycloisomerization of 1‐Bromoalkynes as Key Step
Authors: Miguélez Rubén , Arto Omar , Rodríguez‐Arias Carlos , del Blanco Ángel , Barrio Pablo , González José M. 
Published: December 2023

AbstractGold‐catalyzed cycloisomerization reaction of 1‐bromoalkynes allowed for the preparation of a variety of 1‐bromocyclopentene derivatives. These have been used as substrates in a 3‐step synthetic sequence comprising a cross‐coupling reaction, followed by ozonolysis, and final condensation towards the corresponding 2,5‐disubstituted pyridine. In addition, bicyclic fused pyridines are achieved, including the first total synthesis of the natural product Sinensine B.
Change in pain expectations but no open‐label placebo analgesia: An experimental study using the heat pain paradigm
Authors: Friehs Thilo , Milde Christopher , Glombiewski Julia Anna , Kube Tobias 
Published: December 2023

AbstractBackgroundOpen‐label placebos (OLP) prescribed without deception and with a convincing rationale have been shown to evoke powerful treatment effects. Patients’ treatment expectations seem to influence the magnitude of the effect.ObjectiveWe examined if two different OLP rationales increased pain tolerance and reduced pain intensity and unpleasantness in a standardized heat pain experiment.MethodsParticipants (N = 71) who self‐reported reoccurring pain for at least the last 3 months were randomly assigned to one of three groups. We compared a personal‐emotional and a scientific‐matter‐of‐fact rationale with a control group (CG) that received the same placebo without any rationale. The rationale suggested a desensitizing effect on pain perception and improved pain coping of the placebo, whereas in the CG it was introduced as an ointment for measurement. The primary outcomes were pre–post changes in pain tolerance, expected and experienced pain intensity and unpleasantness.ResultsParticipants showed a decrease in expected pain intensity, but not expected pain unpleasantness for both rationales. There were no differences in pain tolerance and experienced pain intensity and unpleasantness.ConclusionsOur study suggests that evoking positive treatment expectations is not sufficient to elicit an OLP response. Possibly, the magnitude of expectations change in this study was not powerful enough to evoke an OLP effect. Additionally, it is possible that OLP effects in pain are unrelated to positive treatment expectations. The failure of OLP in our study is in contrast to a number of previous studies examining the effects of OLP in experimental and clinical pain.SignificanceThis study provides evidence that positive treatment expectations are not sufficient to evoke an open‐label placebo effect in a standardized heat pain experiment. We showed that two different rationales improved participants treatment expectations, but failed to evoke a placebo effect in comparison to a control group that received the same placebo, labelled as an ointment to improve measurement quality.
Autopsy of a failed trial part 2: Outcomes, challenges, and lessons learnt from the DAISIES trial
Authors: İnce Başak , Phillips Matthew D. , Zenasni Zohra , Shearer James , Dalton Bethan , Irish Madeleine , Mercado Daniela , Webb Hannah , McCombie Catherine , Au Katie , Kern Nikola , Clark‐Stone Sam , Connan Frances , Johnston A. Louise , Lazarova Stanimira , Zadeh Ewa , Newell Ciarán , Pathan Tayeem , Wales Jackie , Cashmore Rebecca , Marshall Sandra , Arcelus Jon , Robinson Paul , Byford Sarah , Landau Sabine , Lawrence Vanessa , Himmerich Hubertus , Treasure Janet , Schmidt Ulrike 
Published: December 2023

AbstractObjectiveThe relative merits of inpatient or day‐treatment for adults with anorexia nervosa (AN) are unknown. The DAISIES trial aimed to establish the non‐inferiority of a stepped‐care day patient treatment (DPT) approach versus inpatient treatment as usual (IP‐TAU) for improving body mass index (BMI) at 12 months in adults with AN. The trial was terminated due to poor recruitment. This paper presents outcomes and investigates the reasons behind the trial's failure.MethodFifteen patients with AN (of 53 approached) participated and were followed‐up to 6 or 12 months. Summary statistics were calculated due to low sample size, and qualitative data concerning treatment experiences were analysed using thematic analysis.ResultsAt baseline, participants in both trial arms rated stepped‐care DPT as more acceptable. At 12 months, participants' BMIs had increased in both trial arms. Qualitative analysis highlighted valued and challenging aspects of care across settings. Only 6/12 sites opened for recruitment. Among patients approached, the most common reason for declining participation was their treatment preference (n = 12/38).ConclusionsNo conclusions can be drawn concerning the effectiveness of IP‐TAU and stepped‐care DPT, but the latter was perceived more positively. Patient‐related, service‐related and systemic factors (COVID‐19) contributed to the trial's failure. Lessons learnt can inform future studies.
Friction effects on connection systems in modern concrete segmental linings
Authors: Oliveira David , Asche Harry , Harding Anthony 
Published: December 2023

AbstractOnce grouted into place and compressed by ground and groundwater, modern segmental linings do not need additional connections except when the lining is required to withstand unusual conditions. Connection systems are provided for two reasons: to assist in the segment‐building process and/or to prevent undesirable actions. A particular focus is on creating and maintaining sufficient gasket compression to seal the lining in the short and long term. The evaluation and design of these connection systems usually involve a simple 1D calculation, ignoring the actual geometry and the presence of other segments and connectors. This study looks at an actual design situation highlighting the role of friction between adjacent segments and the utility of guide rods in the radial joints.
Vegetation destruction during an extreme flood: Multilevel modelling of an entire river in southern Korea
Authors: Lee Keonhak , Lee Cheolho , Baek Donghae , Park Gunwoo , Shim Taeyong , Kim Won , Cho Kang‐Hyun , Kim Daehyun 
Published: December 2023

AbstractHuman‐induced climate change causes extreme weather events, and flooding induced by heavy rainfall in the riparian system is no exception. The southern Korean Peninsula witnessed record‐breaking rainfall during the summer of 2020, resulting in an extreme flood event that caused extensive damage to the riparian ecosystem along the Seomjin River. This study was aimed at identifying the composite factors of riparian vegetation destruction along the entire river. Based on a spatially explicit multilevel approach, it was found that large‐scale geomorphic characteristics (i.e., alternation of plain and valley topographies) appeared to be essential determinants of hydraulic characteristics of the channel (e.g., shear stress and specific energy), which were the leading causes of vegetation destruction. Moreover, at small spatial scales, several trees situated upstream of a vegetation patch protected other plants on the patch from the direct hydraulic impact of the flood, thereby serving as ‘shield’ trees. These findings indicate that scale‐dependent fluvial biogeomorphic processes take place during extreme flood events; hence, identifying the optimal scales of these processes and associated factors could help in further understanding riparian hydrology from a biogeomorphic point of view. This study suggests that hydrologists consider both geomorphological and ecological factors when studying hydrological processes.
Overview of the epidemic characteristics of Mycoplasma pneumoniae infection around COVID pandemic
Authors: Sun Hongmei , Xiao Li 
Published: December 2023

AbstractMycoplasma pneumoniae (M. pneumoniae) is a cell wall‐less respiratory pathogen causing community‐acquired pneumonia and extrapulmonary manifestations. It is transmitted through close contact and shows periodic regional outbreaks. The coronavirus disease (COVID‐19) pandemic interfered with the global spread of M. pneumoniae. A large‐scale post‐COVID outbreak is currently ongoing in China. To help physicians better understand and manage this epidemic, we provide this review summarizing current knowledge on the pathogenesis, epidemic characteristics, macrolide resistance, diagnostic methods, and clinical treatment strategies for this pathogen.
Duck pan‐genome reveals two transposon insertions caused bodyweight enlarging and white plumage phenotype formation during evolution
Authors: Wang Kejun , Hua Guoying , Li Jingyi , Yang Yu , Zhang Chenxi , Yang Lan , Hu Xiaoyu , Scheben Armin , Wu Yanan , Gong Ping , Zhang Shuangjie , Fan Yanfeng , Zeng Tao , Lu Lizhi , Gong Yanzhang , Jiang Ruirui , Sun Guirong , Tian Yadong , Kang Xiangtao , Hu Haifei , Li Wenting 
Published: December 2023

AbstractStructural variations (SVs) are a major source of domestication and improvement traits. We present the first duck pan‐genome constructed using five genome assemblies capturing ∼40.98 Mb new sequences. This pan‐genome together with high‐depth sequencing data (∼46.5×) identified 101,041 SVs, of which substantial proportions were derived from transposable element (TE) activity. Many TE‐derived SVs anchoring in a gene body or regulatory region are linked to duck's domestication and improvement. By combining quantitative genetics with molecular experiments, we, for the first time, unraveled a 6945 bp Gypsy insertion as a functional mutation of the major gene IGF2BP1 associated with duck bodyweight. This Gypsy insertion, to our knowledge, explains the largest effect on bodyweight among avian species (27.61% of phenotypic variation). In addition, we also examined another 6634 bp Gypsy insertion in MITF intron, which triggers a novel transcript of MITF, thereby contributing to the development of white plumage. Our findings highlight the importance of using a pan‐genome as a reference in genomics studies and illuminate the impact of transposons in trait formation and livestock breeding.
Review of electrospun microtube array membrane (MTAM)‐a novel new class of hollow fiber for encapsulated cell therapy (ECT) in clinical applications
Authors: Chew Chee Ho , Lee Hsin‐Lun , Chen Amanda Lin , Huang Wan‐Ting , Chen Shu‐Mei , Liu Yen‐Lin , Chen Chien‐Chung 
Published: December 2023

AbstractEncapsulated cell therapy (ECT) shows significant potential for treating neurodegenerative disorders including Alzheimer's and Parkinson's, which currently lack curative medicines and must be managed symptomatically. This novel technique encapsulates functional cells with a semi‐permeable membrane, providing protection while enabling critical nutrients and therapeutic substances to pass through. Traditional ECT procedures, on the other hand, pose difficulties in terms of cell survival and retrieval. We introduce the Microtube Array Membrane (MTAM), a revolutionary technology that solves these constraints, in this comprehensive overview. Microtube Array Membrane has distinct microstructures that improve encapsulated cells' long‐term viability by combining the advantages of macro and micron scales. Importantly, the MTAM platform improves biosafety by allowing the entire encapsulated unit to be retrieved in the event of an adverse reaction. Our findings show that MTAM‐based ECT has a great potential in a variety of illness situations. For cancer treatment, hybridoma cells secreting anti‐CEACAM 6 antibodies inhibit triple‐negative breast cancer cell lines for an extended period of time. In animal brain models of Alzheimer's disease, hybridoma cells secreting anti‐pTau antibodies successfully reduce pTau buildup, accompanied by improvements in memory performance. In mouse models, MTAM‐encapsulated primary cardiac mesenchymal stem cells dramatically improve overall survival and heart function. These findings illustrate the efficacy and adaptability of MTAM‐based ECT in addressing major issues such as immunological isolation, cell viability, and patient safety. We provide new possibilities for the treatment of neurodegenerative illnesses and other conditions by combining the potential of ECT with MTAM. Continued research and development in this subject has a lot of promise for developing cell therapy and giving hope to people suffering from chronic diseases.