bluuebunny/crossref_metadata_2025_split huggingface dataset:
Real-World Effectiveness of High-Dose Olanzapine and Clozapine for Treatment-Resistant Schizophrenia in Japan
Authors: Watanabe Maiko , Misawa Fuminari , Takeuchi Hiroyoshi 
Published: January 2024

Abstract

Background
Clozapine is considered the gold standard medication for treatment-resistant schizophrenia (TRS). However, given that clozapine treatment is associated with the burden of regular blood monitoring and the risk of life-threatening adverse effects, high-dose olanzapine can serve as an alternative treatment. We conducted a bidirectional mirror-image study to evaluate the effectiveness of high-dose olanzapine compared with clozapine.

Methods
We included patients with TRS who switched from olanzapine to clozapine or switched from clozapine to olanzapine, and received high-dose (>20 mg/d) olanzapine treatment for ≥4 weeks at Yamanashi Prefectural Kita Hospital. We obtained data on hospitalization, seclusion, and modified electroconvulsive therapy (mECT) during the clozapine phase and the olanzapine phase.

Results
A total of 44 patients were included. When patients switched from high-dose olanzapine to clozapine (n = 32), significant reductions were found in the total days of seclusion, the total number of mECT, and the number of patients who received mECT at least once. When patients switched from clozapine to high-dose olanzapine (n = 12), a significant reduction was found in the number of patients who received mECT at least once. When data from both directions of treatment were combined, significant reductions were found in the total days of seclusion, the total number of mECT, and the number of patients who received mECT at least once in favor of clozapine.

Conclusions
Findings suggest that high-dose olanzapine may not be as effective as clozapine for patients with TRS in real-world practice. However, it should be noted that there are unique circumstances that restrict the use of clozapine in Japan.
microRNAs and thrombo-inflammation: relationship in sight
Authors: Águila Sonia , González-Conejero Rocío , Martínez Constantino 
Published: January 2024

Purpose of review
Thrombo-inflammation is a multifaceted pathologic process involving various cells such as platelets, neutrophils, and monocytes. In recent years, microRNAs have been consistently implicated as regulators of these cells.

Recent findings
MicroRNAs play a regulatory role in several platelet receptors that have recently been identified as contributing to thrombo-inflammation and neutrophil extracellular trap (NET) formation. In addition, a growing body of evidence has shown that several intracellular and extracellular microRNAs directly promote NET formation.

Summary
Targeting microRNAs is a promising therapeutic approach to control thrombosis in patients with both infectious and noninfectious inflammatory diseases. Future research efforts should focus on elucidating the specific roles of microRNAs in thrombo-inflammation and translating these findings into tangible benefits for patients.
Impact of Preoperative Diabetes Mellitus on Postoperative Outcomes in Elective Pancreatic Surgery and Its Implications for Prehabilitation Practice
Authors: Wijma Allard G. , Driessens Heleen , Nijkamp Maarten W. , Hoogwater Frederik J.H. , van Dijk Peter R. , Klaase Joost M. 
Published: January 2024

Objectives
Patients with pancreatic disease(s) have a high risk of developing diabetes mellitus (DM). Diabetes mellitus is associated with adverse postoperative outcomes. This study aimed to investigate the prevalence and effects of DM on postoperative outcomes in pancreatic surgery.

Methods
Subgroup analysis of a prospective cohort study conducted at an academic hospital. Patients undergoing pancreatoduodenectomy between January 2019 and November 2022 were included and screened for DM preoperatively using glycated hemoglobin (HbA1c). New-onset DM was diagnosed based on HbA1c ≥ 6.5% (48 mmol/mol). Postoperative outcomes were compared between patients with and without DM.

Results
From 117 patients, 29 (24.8%) were given a diagnosis of DM, and of those, 5 (17.2%) were diagnosed with new-onset DM, and 15 (51.8%) displayed poorly controlled preoperative DM (HbA1c ≥ 7% [53 mmol/mol]). The incidence of surgical site infections (48.3% vs 27.3% in the non-DM group; P = 0.04) was higher for patients with DM. This association remained significant after adjusting for confounders (odds ratio, 2.60 [95% confidence interval, 1.03–6.66]; P = 0.04).

Conclusions
One-quarter of the patients scheduled for pancreatoduodenectomy had DM; over half of them had poor glycemic control. The association between DM status and surgical site infections revealed in this study emphasizes the importance of adequate preoperative glycemic control.
Cell of Origin of Pancreatic cancer
Authors: Zheng Chenlei , Wang Jianing , Wang Junli , Zhang Qi , Liang Tingbo 
Published: January 2024

Abstract
Pancreatic ductal adenocarcinoma (PDAC) stands as one of the most lethal diseases globally, boasting a grim 5-year survival prognosis. The origin cell and the molecular signaling pathways that drive PDAC progression are not entirely understood. This review comprehensively outlines the categorization of PDAC and its precursor lesions, expounds on the creation and utility of genetically engineered mouse models used in PDAC research, compiles a roster of commonly used markers for pancreatic progenitors, duct cells, and acinar cells, and briefly addresses the mechanisms involved in the progression of PDAC. We acknowledge the value of precise markers and suitable tracing tools to discern the cell of origin, as it can facilitate the creation of more effective models for PDAC exploration. These conclusions shed light on our existing understanding of foundational genetically engineered mouse models and focus on the origin and development of PDAC.
Comparison of dolutegravir and efavirenz on depression, anxiety and sleep disorders in pregnant and postpartum women living with HIV
Authors: van der Wekken-Pas Lena , Nassiwa Sylvia , Malaba Thokozile , Lamorde Mohammed , Myer Landon , Waitt Catriona , Reynolds Helen , Khoo Saye , He Nengjie , van Leeuwen Liesbeth , Burger David , Wang Duolao , Colbers Angela 
Published: January 2024

Background:
Both dolutegravir and efavirenz are known to be effective in pregnancy and postpartum to prevent vertical transmission of HIV and to maintain maternal health. Both drugs have also been associated with neuropsychiatric symptoms. To what extent, these symptoms occur in pregnant and postpartum women, however, is not yet known.

Methods:
This was a secondary analysis of the DolPHIN2 study, a multicentre randomized trial among women presenting late in pregnancy with untreated HIV – who received either a dolutegravir-containing or efavirenz-containing regimen. Longitudinal measures of depression, anxiety and sleep quality were analysed during pregnancy and up to 48 weeks postpartum.

Results:
Among 268 women, median (IQR) Edinburgh Post Natal Depression Score (EPDS) scores were 8 (3–11) and highest at enrolment. In the dolutegravir and efavirenz arm, respectively, 23.7 and 25.6% had an EPDS score above 9, indicating possible or probable depression. Abnormal Hospital Anxiety Depression scores (HADS) (above 11) were seen at least once during follow-up in 42 of patients (15.7%), although no differences were seen between treatment arms. No association was found between EPDS, suicidality and HADS scores and the assigned regimen (P = 0.93, 0.97 and 0.18 respectively). Median (IQR) Pittsburgh Sleep Quality index (PSQI) scores for dolutegravir and efavirenz were 6 (5–7) and 5 (5–6.5), respectively, P = 0.70.

Conclusion:
No statistically significant differences were observed between efavirenz-containing or dolutegravir-containing regimens. Rates of depression were high, but decreased over the course of time and confirm the need for psychological support after initial HIV diagnosis in pregnancy.
Rescreening on RBANS Delayed Memory Index? Forget About It!
Authors: Sabbagh Marwan N. , Michalak Wojciech , Thim Hansen Charlotte , Ahmad Wichmann Christian , Clark Alice 
Published: January 2024

Objective:
To assess the value of rescreening patients with Alzheimer’s disease who do not meet the inclusion criteria for the Repeatable Battery for the Assessment of Neuropsychological Status Delayed Memory Index (RBANS DMI) at the initial assessment.

Patients and Methods:
Participants (aged 50–85 years, without dementia, Mini-Mental State Examination score ≥22, valid Clinical Dementia Rating [CDR] global score, and amyloid status at baseline) were identified in the European Prevention of Alzheimer’s Dementia database. Changes from baseline in RBANS DMI were estimated using a mixed model for repeated measurements. Logistic regressions were used to estimate the probability of participants with baseline RBANS DMI 86–95 having RBANS DMI ≤85, CDR global score ≥0.5, and amyloid positivity at 6 and 12 months.

Results:
There was significant variability in the change in RBANS DMI scores over time (median change at 6 months: 2.0). An estimated 15% of participants with RBANS DMI 86–95 at baseline progressed to ≤85 at 6 months; 8% also achieved CDR global score ≥0.5 and 5% were also amyloid positive.

Conclusions:
The results from our analysis indicate that there is limited value in rescreening patients based on their initial RBANS DMI score.
The Therapeutic Role of Intermittent Theta Burst Stimulation in Schizophrenia
Authors: Salabat Dorsa , Pourebrahimi Amirali , Mayeli Mahsa , Cattarinussi Giulia 
Published: January 2024

Abstract
Schizophrenia affects approximately 1% of the population worldwide. Multifactorial reasons, ranging from drug resistance to adverse effects of medications, have necessitated exploring further therapeutic options. Intermittent theta burst stimulation (iTBS) is a novel high-frequency form of transcranial magnetic stimulation, a safe procedure with minor adverse effects with faster and longer-lasting poststimulation effects with a potential role in treating symptoms; however, the exact target brain regions and symptoms are still controversial. Therefore, we aimed to systematically investigate the current literature regarding the therapeutic utilities of iTBS using Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines. Twelve studies were included among which 9 found iTBS effective to some degree. These studies targeted the dorsolateral prefrontal cortex and the midline cerebellum. We performed a random-effects meta-analysis on studies that compared the effects of iTBS on schizophrenia symptoms measured by the Positive and Negative Syndrome Scale (PANSS) to sham treatment. Our results showed no significant difference between iTBS and sham in PANSS positive and negative scores, but a trend-level difference in PANSS general scores (k = 6, P = 0.07), and a significant difference in PANSS total scores (k = 6, P = 0.03). Analysis of the studies targeting the dorsolateral prefrontal cortex showed improvement in PANSS negative scores (k = 5, standardized mean difference = −0.83, P = 0.049), but not in PANSS positive scores. Moderators (intensity, pulse, quality, sessions) did not affect the results. However, considering the small number of studies included in this meta-analysis, future works are required to further explore the effects of these factors and also find optimum target regions for positive symptoms.
Polymer-extracted structure of the mechanosensitive channel MscS reveals the role of protein-lipid interactions in the gating cycle
Authors: Moller Elissa , Britt Madolyn , Zhou Fei , Yang Hyojik , Anshkin Andriy , Ernst Robert , Sukharev Sergei , Matthies Doreen 
Published: January 2024

AbstractMembrane protein structure determination is not only technically challenging but is further complicated by the removal or displacement of lipids, which can result in non-native conformations or a strong preference for certain states at the exclusion of others. This is especially applicable to mechanosensitive channels (MSC’s) that evolved to gate in response to subtle changes in membrane tension transmitted through the lipid bilayer.E. coliMscS, a model bacterial system, is an ancestral member of the large family of MSCs found across all phyla of walled organisms. As a tension sensor, MscS is very sensitive and highly adaptive; it readily opens under super-threshold tension and closes under no tension, but under lower tensions, it slowly inactivates and can only recover when tension is released. However, existing cryo-EM structures do not explain the entire functional gating cycle of open, closed, and inactivated states. A central question in the field has been the assignment of the frequently observed non-conductive conformation to either a closed or inactivated state. Here, we present a 3 Å MscS structure in native nanodiscs obtained with Glyco-DIBMA polymer extraction, eliminating the lipid removal step that is common to all previous structures. Besides the protein in the non-conductive conformation, we observe well-resolved densities of four endogenous phospholipid molecules intercalating between the lipid-facing and pore-lining helices in preferred orientations. Mutations of positively charged residues coordinating these lipids inhibit MscS inactivation, whereas removal of a negative charge near the lipid-filled crevice increases inactivation. The functional data allows us to assign this class of structures to the inactivated state. This structure reveals preserved lipids in their native locations, and the functional effects of their destabilization illustrate a novel inactivation mechanism based on an uncoupling of the peripheral tension-sensing helices from the gate.
Dose range-finding toxicity study in rats with recombinant human lactoferrin produced inKomagataella phaffii
Authors: Peterson Ross , Crawford Robert B. , Blevins Lance K. , Kaminski Norbert E. , Sass June S. , Ferraro Bryce , Vishwanath-Deutsch Roma , Clark Anthony J. , Malinczak Carrie-Anne 
Published: January 2024

ABSTRACTThe oral toxicity of recombinant human lactoferrin (Helaina rhLF, Effera™) produced inKomagataella phaffiiwas investigated in adult Sprague-Dawley rats by once daily oral gavage for 14 consecutive days. The study used groups of 3-6 rats/sex/dose. The vehicle control group received sodium citrate buffer and the test groups received daily doses of 200, 1000 and 2000 mg of rhLF per kg body weight. Bovine LF at 2000 mg/kg body weight per day was used as a comparative control. Clinical observations, body weight, hematology, clinical chemistry, iron parameters, immunophenotyping, and gross examination at necropsy were used as criteria for detecting the effects of treatment in all groups and to inform dose levels for future toxicology studies. Quantitative LF levels were also analyzed as an indication of bioavailability. Overall, administration of Helaina rhLF by once daily oral gavage for 14 days was well tolerated in rats at levels up to 2000 mg/kg/day, or 400x Helaina’s intended commercial use, and indicating that a high dose of 2000 mg/kg/day is appropriate for future definitive toxicology studies.
Bridging DNA contacts allow Dps fromE. colito condense DNA
Authors: Shahu Sneha , Vtyurina Natalia , Das Moumita , Meyer Anne S. , Ganji Mahipal , Abbondanzieri Elio A. 
Published: January 2024

AbstractThe DNA-binding protein from starved cells (Dps) plays a crucial role in maintaining bacterial cell viability during periods of stress. Dps is a nucleoid-associated protein that interacts with DNA to create biomolecular condensates in live bacteria. Purified Dps protein can also rapidly form large complexes when combined with DNAin vitro. However, the mechanism that allows these complexes to nucleate on DNA remains unclear. Here, we examine how DNA topology influences the formation of Dps-DNA complexes. We find that DNA supercoils offer the most preferred template for the nucleation of condensed Dps structures. More generally, bridging contacts between different regions of DNA can facilitate the nucleation of condensed Dps structures. In contrast, Dps shows little affinity for stretched linear DNA before it is relaxed. Once DNA is condensed, Dps forms a stable complex that can form inter-strand contacts with nearby DNA, even without free Dps present in solution. Taken together, our results establish the important role played by bridging contacts between DNA strands in nucleating and stabilizing Dps complexes.Graphical AbstractGraphical Abstract.Working model of nucleation and formation of Dps-DNA complex.Regions of supercoiled or stochastically bent DNA act as nucleation points for the formation of Dps-DNA complexes by allowing Dps to form bridging contacts. Dps does not readily bind to straight stretches of DNA in isolation. Once Dps-DNA complexes are formed they can form bridging contacts to bind additional DNA.
Jointly benchmarking small and structural variant calls with vcfdist
Authors: Dunn Tim , Zook Justin M. , Holt James M. , Narayanasamy Satish 
Published: January 2024

AbstractIn this work, we extend vcfdist to be the first variant call benchmarking tool to jointly evaluate phased single-nucleotide polymorphisms (SNPs), small insertions/deletions (INDELs), and structural variants (SVs) for the whole genome. First, we find that a joint evaluation of small and structural variants uniformly reduces measured errors for SNPs (−28.9%), INDELs (−19.3%), and SVs (−52.4%) across three datasets. Next, we correct a common flaw in phasing evaluations, reducing measured flip errors by over 50%. Lastly, we show that vcfdist is more accurate than previously published works and on par with the newest approaches, but with improved result interpretability.
Large language models overcome the challenges of unstructured text data in ecology
Authors: Castro Andry , Pinto João , Reino Luís , Pipek Pavel , Capinha César 
Published: January 2024

AbstractThe vast volume of currently available unstructured text data, such as research papers, news, and technical report data, shows great potential for ecological research. However, manual processing of such data is labour-intensive, posing a significant challenge. In this study, we aimed to assess the application of three state-of-the-art prompt-based large language models (LLMs), GPT 3.5, GPT 4, and LLaMA-2-70B, to automate the identification, interpretation, extraction, and structuring of relevant ecological information from unstructured textual sources. We focused on species distribution data from two sources: news outlets and research papers. We assessed the LLMs for four key tasks: classification of documents with species distribution data, identification of regions where species are recorded, generation of geographical coordinates for these regions, and supply of results in a structured format. GPT 4 consistently outperformed the other models, demonstrating a high capacity to interpret textual data and extract relevant information, with the percentage of correct outputs often exceeding 90% (average accuracy across tasks: 87–100%). Its performance also depended on the data source type and task, with better results achieved with news reports, in the identification of regions with species reports and presentation of structured output. Its predecessor, GPT 3.5, exhibited reasonably low accuracy across all tasks and data sources (average accuracy across tasks: 81–97%), whereas LLaMA-2-70B showed the worst performance (37– 73%). These results demonstrate the potential benefit of integrating prompt-based LLMs into ecological data assimilation workflows as essential tools to efficiently process large volumes of textual data.
Selection of different parameters to study epistatic effect between heat shock and slightly deleterious mutations in the most fragile stage of embryogenesisCyprinus carpioL
Authors: Kuzmin Aleksandr , Skripskaya Viktoria , Lobanova Valeria , Brodovaya Polina , Tarasova Alina , Popadin Konstantin , Mikhailova Alina G. , Kozenkova Elena , Mugue Nikolai , Vinogradov Evgenii , Balashov Dmitrii 
Published: January 2024

AbstractThe primary genetic challenge encountered in artificial populations lies in the strong genetic drift, which leads to the accumulation of numerous slightly deleterious mutations across the genome. Such mutations diminish the adaptability of the entire population. The objective of this project involves the investigation and implementation of genetic selection methods within cultivated fish populations suchCyprinus carpio L. In order to maintain a high level of genome quality in productive species, we conducted a proof-of-principle experiment employing stress-induced strong purifying selection. This selection process is based on negative epistasis and effectively eliminates organisms carrying an excess of deleterious variants. The first step involves the creation of mutant and intact groups of fish. To obtain mutant groups, we treated male gametes with the ENU mutagen, which primarily induces single-nucleotide substitutions uniformly throughout the genome, thereby imitating natural mutations. This methodology is paramount for the accurate interpretation of experimental outcomes. Notably, temperature stands as a pivotal factor influencing the embryonic development of fish. Therefore, we subjected the embryos to a diverse range of temperatures and varied the duration of exposure during critical stages of embryogenesis. Through meticulous examination, we ascertained that the stage most susceptible to screening purposes is the 22-somite pair stage, occurring at a temperature of 38°C, with a 40-minute exposure period. We suppose, this comprehensive approach can be applied to improve the quality of the gene pool within domestic fish populations, ultimately enhancing the economic efficacy of fish farms. The future prospects of this method encompass its potential application to various species.
Unravelled proteins form blobs during translocation across nanopores
Authors: Sauciuc Adina , Whittaker Jacob , Tadema Matthijs , Tych Kasia , Guskov Albert , Maglia Giovanni 
Published: January 2024

AbstractThe electroosmotic-driven transport of unravelled proteins across nanopores is an important biological process that is now under investigation for the rapid analysis and sequencing of proteins. For this approach to work, however, it is crucial that the polymer is threaded in single file. Here we found that, contrary to the electrophoretic transport of charged polymers such as DNA, during polypeptide translocation blob-like structures typically form inside nanopores. Comparisons between different nanopore sizes, shapes and surface chemistries showed that under electroosmotic-dominated regimes single-file transport of polypeptides can be achieved using nanopores that simultaneously have an entry and an internal diameter that is smaller than the persistence length of the polymer, have a uniform non-sticky (i.e. non-aromatic) nanopore inner surface, and using moderate translocation velocities.