bluuebunny/crossref_metadata_2025_split huggingface dataset:
Adjuvant chemotherapy for adenocarcinoma arising from intraductal papillary mucinous neoplasia: multicentre ADENO-IPMN study
Authors: Lucocq James , Hawkyard Jake , Haugk Beate , Mownah Omar , Menon Krishna , Furukawa Takaki , Inoue Yosuke , Hirose Yuki , Sasahira Naoki , Feretis Michael , Balakrishnan Anita , Ceresa Carlo , Davidson Brian , Pande Rupaly , Dasari Bobby , Tanno Lulu , Karavias Dimitrios , Helliwell Jack , Young Alistair , Nunes Quentin , Urbonas Tomas , Silva Michael , Gordon-Weeks Alex , Barrie Jenifer , Gomez Dhanny , Van Laarhoven Stijn , Robertson Francis , Nawara Hossain , Doyle Joseph , Bhogal Ricky , Harrison Ewen , Roalso Marcus , Ciprani Debora , Aroori Somaiah , Ratnayake Bathiya , Koea Jonathan , Capurso Gabriele , Bellotti Ruben , Stättner Stefan , Alsaoudi Tareq , Bhardwaj Neil , Rajesh Srujan , Jeffery Fraser , Connor Saxon , Cameron Andrew , Jamieson Nigel , Sheen Amy , Mittal Anubhav , Samra Jas , Gill Anthony , Roberts Keith , Søreide Kjetil , Pandanaboyana Sanjay 
Published: April 2024

Abstract

Background
The clinical impact of adjuvant chemotherapy after resection for adenocarcinoma arising from intraductal papillary mucinous neoplasia is unclear. The aim of this study was to identify factors related to receipt of adjuvant chemotherapy and its impact on recurrence and survival.

Methods
This was a multicentre retrospective study of patients undergoing pancreatic resection for adenocarcinoma arising from intraductal papillary mucinous neoplasia between January 2010 and December 2020 at 18 centres. Recurrence and survival outcomes for patients who did and did not receive adjuvant chemotherapy were compared using propensity score matching.

Results
Of 459 patients who underwent pancreatic resection, 275 (59.9%) received adjuvant chemotherapy (gemcitabine 51.3%, gemcitabine–capecitabine 21.8%, FOLFIRINOX 8.0%, other 18.9%). Median follow-up was 78 months. The overall recurrence rate was 45.5% and the median time to recurrence was 33 months. In univariable analysis in the matched cohort, adjuvant chemotherapy was not associated with reduced overall (P = 0.713), locoregional (P = 0.283) or systemic (P = 0.592) recurrence, disease-free survival (P = 0.284) or overall survival (P = 0.455). Adjuvant chemotherapy was not associated with reduced site-specific recurrence. In multivariable analysis, there was no association between adjuvant chemotherapy and overall recurrence (HR 0.89, 95% c.i. 0.57 to 1.40), disease-free survival (HR 0.86, 0.59 to 1.30) or overall survival (HR 0.77, 0.50 to 1.20). Adjuvant chemotherapy was not associated with reduced recurrence in any high-risk subgroup (for example, lymph node-positive, higher AJCC stage, poor differentiation). No particular chemotherapy regimen resulted in superior outcomes.

Conclusion
Chemotherapy following resection of adenocarcinoma arising from intraductal papillary mucinous neoplasia does not appear to influence recurrence rates, recurrence patterns or survival.
Revisiting distinct nerve excitability patterns in patients with amyotrophic lateral sclerosis
Authors: Stikvoort García Diederik J L , Goedee H Stephan , van Eijk Ruben P A , van Schelven Leonard J , van den Berg Leonard H , Sleutjes Boudewijn T H M 
Published: April 2024

Abstract
Amyotrophic lateral sclerosis is a devastating neurodegenerative disease, characterized by loss of central and peripheral motor neurons. Although the disease is clinically and genetically heterogeneous, axonal hyperexcitability is a commonly observed feature that has been suggested to reflect an early pathophysiological step linked to the neurodegenerative cascade. Therefore, it is important to clarify the mechanisms causing axonal hyperexcitability and how these relate to the clinical characteristics of patients.
Measures derived directly from a nerve excitability recording are frequently used as study end points, although their biophysical basis is difficult to deduce. Mathematical models can aid in the interpretation but are reliable only when applied to group-averaged recordings. Consequently, model estimates of membrane properties cannot be compared with clinical characteristics or treatment effects in individual patients, posing a considerable limitation in heterogeneous diseases, such as amyotrophic lateral sclerosis. To address these challenges, we revisited nerve excitability using a new pattern analysis-based approach (principal component analysis). We evaluated disease-specific patterns of excitability changes and established their biophysical origins. Based on the observed patterns, we developed new compound measures of excitability that facilitate the implementation of this approach in clinical settings.
We found that excitability changes in amyotrophic lateral sclerosis patients (n = 161, median disease duration = 11 months) were characterized by four unique patterns compared with controls (n = 50, age and sex matched). These four patterns were best explained by changes in resting membrane potential (modulated by Na+/K+ currents), slow potassium and sodium currents (modulated by their gating kinetics) and refractory properties of the nerve. Consequently, we were able to show that altered gating of slow potassium channels was associated with, and predictive of, the rate of progression of the disease on the amyotrophic lateral sclerosis functional rating scale. Based on these findings, we designed four composite measures that capture these properties to facilitate implementation outside this study.
Our findings demonstrate that changes in nerve excitability in patients with amyotrophic lateral sclerosis are dominated by four distinct patterns, each with a distinct biophysical origin. Based on this new approach, we provide evidence that altered slow potassium-channel function might play a role in the rate of disease progression. The magnitudes of these patterns, quantified using a similar approach or our new composite measures, have potential as efficient measures to study membrane properties directly in amyotrophic lateral sclerosis patients, and thus aid prognostic stratification and trial design.
Unleashing the potential of mRNA therapeutics for inherited neurological diseases
Authors: Monfrini Edoardo , Baso Giacomo , Ronchi Dario , Meneri Megi , Gagliardi Delia , Quetti Lorenzo , Verde Federico , Ticozzi Nicola , Ratti Antonia , Di Fonzo Alessio , Comi Giacomo P , Ottoboni Linda , Corti Stefania 
Published: April 2024

AbstractNeurological monogenic loss-of-function diseases are hereditary disorders resulting from gene mutations that decrease or abolish the normal function of the encoded protein. These conditions pose significant therapeutic challenges, which may be resolved through the development of innovative therapeutic strategies. RNA-based technologies, such as mRNA replacement therapy, have emerged as promising and increasingly viable treatments. Notably, mRNA therapy exhibits significant potential as a mutation-agnostic approach that can address virtually any monogenic loss-of-function disease.Therapeutic mRNA carries the information for a healthy copy of the defective protein, bypassing the problem of targeting specific genetic variants. Moreover, unlike conventional gene therapy, mRNA-based drugs are delivered through a simplified process that requires only transfer to the cytoplasm, thereby reducing the mutagenic risks related to DNA integration. Additionally, mRNA therapy exerts a transient effect on target cells, minimizing the risk of long-term unintended consequences. The remarkable success of mRNA technology for developing coronavirus disease 2019 vaccines has rekindled interest in mRNA as a cost-effective method for delivering therapeutic proteins. However, further optimization is required to enhance mRNA delivery, particularly to the CNS, while minimizing adverse drug reactions and toxicity.In this comprehensive review, we delve into past, present and ongoing applications of mRNA therapy for neurological monogenic loss-of-function diseases. We also discuss the promises and potential challenges presented by mRNA therapeutics in this rapidly advancing field. Ultimately, we underscore the full potential of mRNA therapy as a game-changing therapeutic approach for neurological disorders.
Energy model based on solar potential and the production of electrical energy through living plants’ photosynthesis
Authors: Rodriguez Martinez Raymond Daniel 
Published: April 2024

Abstract
Developing a sustainable energy model is imperative considering the current trend towards decarbonizing sectors worldwide. For this purpose, Venezuela was used as a reference to propose an energy model focused on taking advantage of plant photosynthesis through microbial–vegetable fuel cells together with an agro-photovoltaic system to enhance energy and agricultural production. Energy production from the cells was estimated using an average power density of 264 mW/m2 over 4% of the areas destined for crops in the entire Venezuelan region, obtaining an annual production of 19.889 GWh/year. In contrast, the energy production of the agro-photovoltaic system was modelled using PVsyst software on 50% of the area used for the cells distributed throughout the states of Anzoátegui, Guárico, Monagas and Portuguesa according to their meteorological conditions, solar irradiation and agricultural activity, resulting in 3 703 417 GWh/year. The resulting whole system proved to be able to cover &gt;10 times the installed electricity generation capacity at a national level and, together with the tremendous scalability of the microbial fuel cells, it shows that Venezuela has a high potential for the production and distribution of clean energy.
How Does the Proportion of Never Treatment Influence the Success of Mass Drug Administration Programs for the Elimination of Lymphatic Filariasis?
Authors: Kura Klodeta , Stolk Wilma A , Basáñez Maria-Gloria , Collyer Benjamin S , de Vlas Sake J , Diggle Peter J , Gass Katherine , Graham Matthew , Hollingsworth T Déirdre , King Jonathan D , Krentel Alison , Anderson Roy M , Coffeng Luc E 
Published: April 2024

Abstract

Background
Mass drug administration (MDA) is the cornerstone for the elimination of lymphatic filariasis (LF). The proportion of the population that is never treated (NT) is a crucial determinant of whether this goal is achieved within reasonable time frames.

Methods
Using 2 individual-based stochastic LF transmission models, we assess the maximum permissible level of NT for which the 1% microfilaremia (mf) prevalence threshold can be achieved (with 90% probability) within 10 years under different scenarios of annual MDA coverage, drug combination and transmission setting.

Results
For Anopheles-transmission settings, we find that treating 80% of the eligible population annually with ivermectin + albendazole (IA) can achieve the 1% mf prevalence threshold within 10 years of annual treatment when baseline mf prevalence is 10%, as long as NT &lt;10%. Higher proportions of NT are acceptable when more efficacious treatment regimens are used. For Culex-transmission settings with a low (5%) baseline mf prevalence and diethylcarbamazine + albendazole (DA) or ivermectin + diethylcarbamazine + albendazole (IDA) treatment, elimination can be reached if treatment coverage among eligibles is 80% or higher. For 10% baseline mf prevalence, the target can be achieved when the annual coverage is 80% and NT ≤15%. Higher infection prevalence or levels of NT would make achieving the target more difficult.

Conclusions
The proportion of people never treated in MDA programmes for LF can strongly influence the achievement of elimination and the impact of NT is greater in high transmission areas. This study provides a starting point for further development of criteria for the evaluation of NT.
Subnational Projections of Lymphatic Filariasis Elimination Targets in Ethiopia to Support National Level Policy
Authors: Prada Joaquin M , Touloupou Panayiota , Kebede Biruck , Giorgi Emanuelle , Sime Heven , Smith Morgan , Kontoroupis Periklis , Brown Paul , Cano Jorge , Farkas Hajnal , Irvine Mike , Reimer Lisa , Caja Rivera Rocio , de Vlas Sake J , Michael Edwin , Stolk Wilma A , Pulan Rachel , Spencer Simon E F , Hollingsworth T Déirdre , Seife Fikre 
Published: April 2024

Abstract

Background
Lymphatic filariasis (LF) is a debilitating, poverty-promoting, neglected tropical disease (NTD) targeted for worldwide elimination as a public health problem (EPHP) by 2030. Evaluating progress towards this target for national programmes is challenging, due to differences in disease transmission and interventions at the subnational level. Mathematical models can help address these challenges by capturing spatial heterogeneities and evaluating progress towards LF elimination and how different interventions could be leveraged to achieve elimination by 2030.

Methods
Here we used a novel approach to combine historical geo-spatial disease prevalence maps of LF in Ethiopia with 3 contemporary disease transmission models to project trends in infection under different intervention scenarios at subnational level.

Results
Our findings show that local context, particularly the coverage of interventions, is an important determinant for the success of control and elimination programmes. Furthermore, although current strategies seem sufficient to achieve LF elimination by 2030, some areas may benefit from the implementation of alternative strategies, such as using enhanced coverage or increased frequency, to accelerate progress towards the 2030 targets.

Conclusions
The combination of geospatial disease prevalence maps of LF with transmission models and intervention histories enables the projection of trends in infection at the subnational level under different control scenarios in Ethiopia. This approach, which adapts transmission models to local settings, may be useful to inform the design of optimal interventions at the subnational level in other LF endemic regions.
Using Passive Surveillance to Maintain Elimination as a Public Health Problem for Neglected Tropical Diseases: A Model-Based Exploration
Authors: Minter Amanda , Medley Graham F , Hollingsworth T Déirdre 
Published: April 2024

Abstract

Background
Great progress is being made toward the goal of elimination as a public health problem for neglected tropical diseases such as leprosy, human African trypanosomiasis, Buruli ulcer, and visceral leishmaniasis, which relies on intensified disease management and case finding. However, strategies for maintaining this goal are still under discussion. Passive surveillance is a core pillar of a long-term, sustainable surveillance program.

Methods
We use a generic model of disease transmission with slow epidemic growth rates and cases detected through severe symptoms and passive detection to evaluate under what circumstances passive detection alone can keep transmission under control.

Results
Reducing the period of infectiousness due to decreasing time to treatment has a small effect on reducing transmission. Therefore, to prevent resurgence, passive surveillance needs to be very efficient. For some diseases, the treatment time and level of passive detection needed to prevent resurgence is unlikely to be obtainable.

Conclusions
The success of a passive surveillance program crucially depends on what proportion of cases are detected, how much of their infectious period is reduced, and the underlying reproduction number of the disease. Modeling suggests that relying on passive detection alone is unlikely to be enough to maintain elimination goals.
Incorporating otolith-isotope inferred field metabolic rate into conservation strategies
Authors: de Groot Valesca A , Trueman Clive , Bates Amanda E 
Published: April 2024

Abstract
Fluctuating ocean conditions are rearranging whole networks of marine communities—from individual-level physiological thresholds to ecosystem function. Physiological studies support predictions from individual-level responses (biochemical, cellular, tissue, respiratory potential) based on laboratory experiments. The otolith-isotope method of recovering field metabolic rate has recently filled a gap for the bony fishes, linking otolith stable isotope composition to in situ oxygen consumption and experienced temperature estimates. Here, we review the otolith-isotope method focusing on the biochemical and physiological processes that yield estimates of field metabolic rate. We identify a multidisciplinary pathway in the application of this method, providing concrete research goals (field, modeling) aimed at linking individual-level physiological data to higher levels of biological organization. We hope that this review will provide researchers with a transdisciplinary ‘roadmap’, guiding the use of the otolith-isotope method to bridge the gap between individual-level physiology, observational field studies, and modeling efforts, while ensuring that in situ data is central in marine policy-making aimed at mitigating climatic and anthropogenic threats.
Gamma delta (γδ) T cells in the female reproductive tract: active participants or indifferent bystanders in reproductive success?
Authors: Foyle Kerrie L , Robertson Sarah A 
Published: April 2024

Summary
The female reproductive tract accommodates and balances the unique immunological challenges of protection from sexually transmitted pathogens and tolerance of the fetus and placenta in pregnancy. Leukocytes in the female reproductive tract actively engage in extensive maternal adaptations that are imperative for embryo implantation, placental development, and fetal growth support. γδ T cells are abundant at many mucosal sites in the body, where they provide protection against pathogens and cancer, and have roles in tissue renewal and homeostasis. In this review, we summarize studies in humans and rodents showing that γδ T cells are prevalent in the female reproductive tract and fluctuate in response to hormone changes across the reproductive cycle. Emerging evidence points to a link between changes in their abundance and molecular repertoire in the uterus and pregnancy disorders including recurrent miscarriage and preterm birth. However, defining the precise functional role of female reproductive tract γδ T cells and understanding their physiological significance in reproduction and pregnancy have remained elusive. Here, we critically analyze whether reproductive tract γδ T cells could be active participants in reproductive events—or whether their principal function is immune defense, in which case they may compromise pregnancy success unless adequately regulated.
Dyslipidaemia management in pregnant patients: a 2024 update
Authors: Lewek Joanna , Bielecka-Dąbrowa Agata , Toth Peter P , Banach Maciej 
Published: April 2024

Abstract
Over several decades, the approach to treating dyslipidaemias during pregnancy remains essentially unchanged. The lack of advancement in this field is mostly related to the fact that we lack clinical trials of pregnant patients both with available as well as new therapies. While there are numerous novel therapies developed for non-pregnant patients, there are still many limitations in dyslipidaemia treatment during pregnancy. Besides pharmacotherapy and careful clinical assessment, the initiation of behavioural modifications as well as pre-conception management is very important. Among the various lipid-lowering medications, bile acid sequestrants are the only ones officially approved for treating dyslipidaemia in pregnancy. Ezetimibe and fenofibrate can be considered if their benefits outweigh potential risks. Statins are still considered contraindicated, primarily due to animal studies and human case reports. However, recent systematic reviews and meta-analyses as well as data on familial hypercholesterolaemia (FH) in pregnant patients have indicated that their use may not be harmful and could even be beneficial in certain selected cases. This is especially relevant for pregnant patients at very high cardiovascular risk, such as those who have already experienced an acute cardiovascular event or have homozygous or severe forms of heterozygous FH. In these cases, the decision to continue therapy during pregnancy should weigh the potential risks of discontinuation. Bempedoic acid, olezarsen, evinacumab, evolocumab and alirocumab, and inclisiran are options to consider just before and after pregnancy is completed. In conclusion, decisions regarding lipid-lowering therapy for pregnant patients should be personalized. Despite the challenges in designing and conducting studies in pregnant women, there is a strong need to establish the safety and efficacy of dyslipidaemia treatment during pregnancy.
Personnel Management and School Productivity: Evidence from India
Authors: Lemos Renata , Muralidharan Karthik , Scur Daniela 
Published: April 2024

AbstractThis paper uses new data to study school management and productivity in India. We report five main results. First, management quality in public schools is low, and ∼2 standard deviations below high-income countries with comparable data. Second, private schools have higher management quality, driven by much stronger people management. Third, people management quality is correlated with independent measures of teaching practice, as well as school productivity measured by student value added. Fourth, better-managed schools have lower variation in within-school teacher effectiveness and higher levels of minimum teacher effectiveness. Fifth, consistent with better people management, teacher pay in private schools is positively correlated with teacher effectiveness, whereas we find no such correlation in public schools.
Robotic thymectomy in thymic tumours: a multicentre, nation-wide study
Authors: Comacchio Giovanni Maria , Schiavon Marco , Zirafa Carmelina Cristina , De Palma Angela , Scaramuzzi Roberto , Meacci Elisa , Bongiolatti Stefano , Monaci Nicola , Lyberis Paraskevas , Novellis Pierluigi , Brandolini Jury , Parini Sara , Ricciardi Sara , D’Andrilli Antonio , Bottoni Edoardo , Gallina Filippo Tommaso , Marino Maria Carlotta , Lorenzoni Giulia , Francavilla Andrea , Rendina Erino Angelo , Cardillo Giuseppe , Rena Ottavio , Solli Piergiorgio , Alloisio Marco , Luzzi Luca , Facciolo Francesco , Voltolini Luca , Margaritora Stefano , Curcio Carlo , Marulli Giuseppe , Ruffini Enrico , Veronesi Giulia , Melfi Franca , Rea Federico 
Published: April 2024

Abstract

OBJECTIVES
Robotic thymectomy has been suggested and considered technically feasible for thymic tumours. However, because of small-sample series and the lack of data on long-term results, controversies still exist on surgical and oncological results with this approach. We performed a large national multicentre study sought to evaluate the early and long-term outcomes after robot-assisted thoracoscopic thymectomy in thymic epithelial tumours.

METHODS
All patients with thymic epithelial tumours operated through a robotic thoracoscopic approach between 2002 and 2022 from 15 Italian centres were enrolled. Demographic characteristics, clinical, intraoperative, postoperative, pathological and follow-up data were retrospectively collected and reviewed.

RESULTS
There were 669 patients (307 men and 362 women), 312 (46.6%) of whom had associated myasthenia gravis. Complete thymectomy was performed in 657 (98%) cases and in 57 (8.5%) patients resection of other structures was necessary, with a R0 resection in all but 9 patients (98.6%). Twenty-three patients (3.4%) needed open conversion, but no perioperative mortality occurred. Fifty-one patients (7.7%) had postoperative complications. The median diameter of tumour resected was 4 cm (interquartile range 3–5.5 cm), and Masaoka stage was stage I in 39.8% of patients, stage II in 56.1%, stage III in 3.5% and stage IV in 0.6%. Thymoma was observed in 90.2% of patients while thymic carcinoma occurred in 2.8% of cases. At the end of the follow-up, only 2 patients died for tumour-related causes. Five- and ten-year recurrence rates were 7.4% and 8.3%, respectively.

CONCLUSIONS
Through the largest collection of robotic thymectomy for thymic epithelial tumours we demonstrated that robot-enhanced thoracoscopic thymectomy is a technically sound and safe procedure with a low complication rate and optimal oncological outcomes.