bluuebunny/crossref_metadata_2025 huggingface dataset:
Working with an instructional video on mathematical modeling: upper-secondary students’ perceived advantages and challenges
Authors: Wirth Laura , Greefrath Gilbert
Published: February 2024

Many instructional videos in mathematics education target knowledge of procedures and algorithms. To design instructional videos that support students in a non-algorithmic domain, such as mathematical modeling, we developed a framework based on research on heuristic worked examples and instructional videos. Because students’ perceptions play an important role in whether they will engage with a learning resource, our research questions focus on the advantages and challenges students perceive when they work with an instructional video on mathematical modeling and solve a subsequent related modeling problem. Using a video based on the developed framework, we conducted an interview study with 14 pairs of upper-secondary students. The results of the qualitative text analysis showed that the perceived advantages and challenges were related to certain design features and to the processes of self-regulated learning with the video. The students experienced challenges regarding the video’s duration, the transfer to a subsequent related modeling problem, the absence of a teacher, and self-discipline. Hence, further learner support is necessary to guide the transition from working with a video to autonomous modeling, such as combining the video with strategic instruments and teacher support. In addition, interactive video features may be essential, as the students enjoyed how those features involved them in the process of watching the video. Overall, the results indicate that instructional videos are promising for providing heuristic worked examples, offering an innovative approach for teaching and learning mathematical modeling.
Network Representation of fMRI Data Using Visibility Graphs: The Impact of Motion and Test-Retest Reliability
Authors: Poudel Govinda R. , Sharma Prabin , Lorenzetti Valentina , Parsons Nicholas , Cerin Ester
Published: February 2024

Visibility graphs provide a novel approach for analysing time-series data. Graph theoretical analysis of visibility graphs can provide new features for data mining applications in fMRI. However, visibility graphs features have not been used widely in the field of neuroscience. This is likely due to a lack of understanding of their robustness in the presence of noise (e.g., motion) and their test-retest reliability. In this study, we investigated visibility graph properties of fMRI data in the human connectome project (N = 1010) and tested their sensitivity to motion and test-retest reliability. We also characterised the strength of connectivity obtained using degree synchrony of visibility graphs. We found that strong correlation (r > 0.5) between visibility graph properties, such as the number of communities and average degrees, and motion in the fMRI data. The test-retest reliability (Intraclass correlation coefficient (ICC)) of graph theoretical features was high for the average degrees (0.74, 95% CI = [0.73, 0.75]), and moderate for clustering coefficient (0.43, 95% CI = [0.41, 0.44]) and average path length (0.41, 95% CI = [0.38, 0.44]). Functional connectivity between brain regions was measured by correlating the visibility graph degrees. However, the strength of correlation was found to be moderate to low (r < 0.35). These findings suggest that even small movement in fMRI data can strongly influence robustness and reliability of visibility graph features, thus, requiring robust motion correction strategies prior to data analysis. Further studies are necessary for better understanding of the potential application of visibility graph features in fMRI.
Strategies and Barriers to Reconcile Pest Management with Insect Conservation in Temperate and Boreal Forests
Authors: Gazzea Elena , Battisti Andrea , Marini Lorenzo
Published: February 2024

Purpose of Review

To describe how general prescriptions to protect temperate and boreal forests against pests have been affecting the conservation of insect diversity, (2) to identify potential conflicts between biodiversity conservation actions and pest control, and (3) to provide future directions to reconcile forest pest management with insect conservation.

Recent Findings

Despite dealing with the same habitats and organisms, forest pest management and insect conservation have been separate disciplines, often pursuing conflicting goals. However, there is a large intersection between the two, as interventions to control pests can have repercussions on biodiversity and vice versa. In several regions, forest pest management is shifting from reactive measures to contain on-going outbreaks to proactive strategies to create forest landscapes that are more resistant and resilient against pests in the long-term. These developments suggest a possible convergence between pest management and insect conservation objectives.

Several reactive measures adopted to control pests can cause negative impacts on non-target insects, although effects are sometimes localized and often context-dependent. Following ecological, economic, and social considerations, pest management has been evolving towards diversifying forests across multiple spatial scales to reduce the severity of outbreaks and the risk of damage. Such strategies concur with multiple conservation goals to increase insect diversity across intensive forest landscapes. Insect conservation has traditionally targeted saproxylic organisms, neglecting the conservation of other insect guilds and seldom assessing side effects on pests. Despite some important knowledge gaps, we propose complementary approaches to combine multiple diversification strategies at the landscape scale to reconcile pest management with insect conservation.
Laser-Induced and MOF-Derived Metal Oxide/Carbon Composite for Synergistically Improved Ethanol Sensing at Room temperature
Authors: Lim Hyeongtae , Kwon Hyeokjin , Kang Hongki , Jang Jae Eun , Kwon Hyuk-Jun
Published: February 2024

Advancements in sensor technology have significantly enhanced atmospheric monitoring. Notably, metal oxide and carbon (MOx/C) hybrids have gained attention for their exceptional sensitivity and room-temperature sensing performance. However, previous methods of synthesizing MOx/C composites suffer from problems, including inhomogeneity, aggregation, and challenges in micropatterning. Herein, we introduce a refined method that employs a metal–organic framework (MOF) as a precursor combined with direct laser writing. The inherent structure of MOFs ensures a uniform distribution of metal ions and organic linkers, yielding homogeneous MOx/C structures. The laser processing facilitates precise micropatterning (< 2 μm, comparable to typical photolithography) of the MOx/C crystals. The optimized MOF-derived MOx/C sensor rapidly detected ethanol gas even at room temperature (105 and 18 s for response and recovery, respectively), with a broad range of sensing performance from 170 to 3,400 ppm and a high response value of up to 3,500%. Additionally, this sensor exhibited enhanced stability and thermal resilience compared to previous MOF-based counterparts. This research opens up promising avenues for practical applications in MOF-derived sensing devices.
The Influence of Filling System Design on Quality Performance in Gray Iron
Authors: Heyworth Robert
Published: February 2024

Significant evidence now supports the quality improvement seen in castings that employ naturally pressurized filling systems in their production. However, despite the documented evidence for improvement, these systems have not become ubiquitous. Gray iron, the industry’s most prominent alloy, has been particularly slow to accept the shift in system design. The suggested tolerability of gray iron to turbulence, the market’s price sensitivity, and the perceived economics of naturally pressurized systems are potential factors that have hindered adoption. However, if, through improved quality, the economic justification for these systems can be made in this adverse setting, there is a merit in their application to all alloys and processes. A sample gray iron part, currently being produced in a foundry environment with known porosity issues, was selected, to which a new system and several basin designs were applied. A mixed method analysis of casting simulations, production trials, and economic and environmental modeling was used to evaluate system performance. The results show a strong association between filling system design and sub-surface porosity. However, no association was found between basin design and porosity occurrence at lower porosity levels. Nevertheless, the economic and environmental modeling highlights that quality-orientated systems yield significant financial and environmental savings for the organization due to reduced scrap levels. These findings imply that quality-orientated system designs should be employed even when cost is the most critical measure.
Regional decline and structural changes in Northeast China: an exploratory space–time approach
Authors: Chen Yilin
Published: February 2024

Literature on New Economic Geography (NEG) highlights the importance of spatial concentration and spillover effects in economic growth or decline. Northeast China, as an old industrial base, is experiencing a regional decline since its transition to the post-industrial stage. Therefore, what is the main sectoral composition in Northeast China and how does this influence regional decline? To what extent do spatial spillovers play a role before and during the regional decline of Northeast China? Based on these questions, we investigated the spatial connections between regional decline and structural changes in Northeast China over three development periods: Rust Belt (1995–2002), revival (2002–2015), and decline (2015–2019). The recent exploratory space–time data analysis was employed on prefecture-level income and its structural change components (sectoral output and employment ratio). We found that the possible reason for the regional decline in Northeast China is premature deindustrialisation. Spatial co-decline in the employment of industry and construction, the primary source of regional decline, facilitates most of the space–time patterns of the regional income. Agglomeration of the agricultural sector has shifted to the north, while industry and construction have gravitated towards the middle and south, with no clear spatial patterns in the service sector. Dependence on natural resources has a "lock-in effect" that inhibits the transition from industry to services, so industry and construction remain the most efficient in Northeast China. Strengthening spatial connections is essential for local governments to develop service sectors and overcome declining conditions.
Characterization and pathogenicity of fungal species associated with hazelnut trunk diseases in North-western Italy
Authors: Martino Ilaria , Monchiero Matteo , Gullino M. Lodovica , Guarnaccia Vladimiro
Published: February 2024

Italy is the second largest hazelnut producer worldwide and Piedmont is one of the most productive regions in the country. The changing climatic condition and fungal trunk diseases (FTD) can have a severe impact on this crop. Particularly, the considerable spread of Cytospora cankers (‘Mal dello stacco’) and dieback represent a serious concern for producers. Thus, considering the limited studies on the causal agents, different surveys were conducted in seven hazelnut orchards during 2021 and 2022. Eight fungal species were identified: Anthostoma decipiens, Botryosphaeria dothidea, Diaporthe eres, Dia. rudis, Diplodia seriata, Dip. subglobosa, Dothiorella parva and Nothophoma brennandiae. Species identification was achieved through multilocus phylogeny and morphology assessment. All the fungal species were pathogenic on healthy hazelnut plants (cultivar Tonda Gentile) and A. decipiens and Dia. eres were the most aggressive. The present study is the first report of B. dothidea and Dia. eres as causal agents of FTD on hazelnut in Italy and of Dia. rudis, Dip. subglobosa and N. brennandiae worldwide. Moreover, the study provides clarification of the fungal pathogens associated with FTD on this crop in Piedmont, thus laying the base for further studies on epidemiology, ecology and management strategies.
Oral intake of bucillamine, carvedilol, metformin, or phenformin does not protect against UVR-induced squamous cell carcinomas in hairless mice
Authors: Pihl Celina , Bjerring Peter , Andersen Flemming , Haedersdal Merete , Lerche Catharina M.
Published: February 2024

Squamous cell carcinoma represents the second most common type of keratinocyte carcinoma with ultraviolet radiation (UVR) making up the primary risk factor. Oral photoprotection aims to reduce incidence rates through oral intake of photoprotective compounds. Recently, drug repurposing has gained traction as an interesting source of chemoprevention. Because of their reported photoprotective properties, we investigated the potential of bucillamine, carvedilol, metformin, and phenformin as photoprotective compounds following oral intake in UVR-exposed hairless mice. Tumour development was observed in all groups in response to UVR, with only the positive control (Nicotinamide) demonstrating a reduction in tumour incidence (23.8%). No change in tumour development was observed in the four repurposed drug groups compared to the UV control group, whereas nicotinamide significantly reduced carcinogenesis (P = 0.00012). Metformin treatment significantly reduced UVR-induced erythema (P = 0.012), bucillamine and phenformin increased dorsal pigmentation (P = 0.0013, and P = 0.0005), but no other photoprotective effect was observed across the repurposed groups. This study demonstrates that oral supplementation with bucillamine, carvedilol, metformin, or phenformin does not affect UVR-induced carcinogenesis in hairless mice.

Graphical Abstract
Case Studies: Stahl's Essential Psychopharmacology
Authors: Strawn Jeffrey R. , Stahl Stephen M.
Published: February 2024

This brand-new fourth volume in Stahl's Case Studies series presents a selection of clinical case studies in child and adolescent psychopharmacology, taken from Dr. Strawn's clinics and consultations. These cases illustrate common questions that are routinely asked by Dr. Strawn's peers in consultations and which represent dilemmas in the day-to-day practice of pediatric psychopharmacology. Followings a consistent, user-friendly layout, each case features icons, tips and questions about diagnosis and management as it progresses over time, a pre-case self-assessment question, followed by the correct answers at the end of the case. Formatted in alignment with the American Board of Psychiatry and Neurology's maintenance of psychiatry speciality certification, cases address multifaceted issues in a relevant and understandable way. Covering a wide-ranging and representative selection of clinical scenarios, each case is followed through the complete clinical encounter, from start to resolution, acknowledging all the complications, issues, decisions, twists and turns along the way.
The Lithium Handbook
Authors: Meyer Jonathan M. , Stahl Stephen M.
Published: February 2024

Worldwide efforts to promote greater lithium use for mood disorders have increased the need for evidence-based guidance addressing key questions related to initiation, monitoring and adverse effect management. This practical handbook provides clinicians with a detailed explanation of lithium's renal journey, how this informs our understanding of polyuria pathogenesis and how medications or hyponatremia can alter lithium clearance. Covering efficacy, pharmacokinetics, toxicity, discontinuation, and use in special patient groups including pregnant and breastfeeding women, older or younger patients, each section also provides a detailed background for its suggested logical approach to managing lithium's renal and other adverse effects. Using the latest data, the book outlines rationales for specific management decisions, and prioritizes options to provide clinical guidance on the best course of action. Colour-coded lists and tables, bulleted text, and diagrams illustrate important points throughout, helping to make information accessible and easy-to-digest. An essential resource for mental health professionals worldwide.
The pope, a knight and a bishop on the edge of Christendom: the politics of exclusion in thirteenth-century Ireland
Authors: Marshall John
Published: February 2024

This article provides a re-appraisal of the land dispute between the lord of Leinster, William Marshal, and the bishop of Ferns, Ailbe Ó Máelmuaid, in the 1210s. In 1215, Ailbe petitioned the pope to solve the dispute, leading to the pronouncement of an interdict and excommunication against the Marshal. It is argued that after King John of England died and the Marshal became regent of England in 1216, the papal stance towards the land dispute changed and the Marshal enjoyed favour in Rome, thus shutting the roads to redress for the bishop of Ferns. Now the most powerful man in the Plantagenet dominions, William Marshal used his position as regent to begin the policy of English discrimination against Gaelic-born bishops for episcopal sees in Ireland. This article uses this dispute as a means of exploring Ireland's position within wider Latin Christendom against the background of the papacy's crusading agenda.
Colonialist intervention in a metropolitan revolution: reconsidering A remonstrance of divers remarkeable passages
Authors: Kelsey Sean
Published: February 2024

This article presents findings from a fresh examination of a familiar source, shedding new light on the creation of one of the best-known contemporary accounts of the 1641 Irish uprising. It is argued that a text usually regarded as the work of Henry Jones, dean of Kilmore, ought to be understood as the intellectual property of both a team of authors and their sponsors, a New English faction at Dublin Castle with long-standing ambitions to crush popery and entrench planter hegemony in Ireland. It is argued that this group's objective was to strengthen the hand of the populist ‘junto’ at Westminster, led by John Pym, that was wrestling with Charles I for political and constitutional supremacy in English affairs in the winter and spring of 1641–2. The colonialists contributed to this metropolitan revolution by rendering safe to handle the Irish rebels’ politically-explosive seditious slander that their uprising had been raised by royal command. The notorious falsehood of the rebels’ claims has obscured the demonstrably underhand and fundamentally deceitful calculation with which the colonialists helped introduce it into mainstream English political culture, in order to isolate the king further and weaken his personal authority on both sides of the Irish Sea.
The Weaver Street bombing in Belfast 1922: violence, politics and memory
Authors: Dobrianska Nadia
Published: February 2024

On 13 February 1922, an unidentified person threw a bomb into Weaver Street, which was full of Catholic children at play, killing four children and two women. The bombing became a locus of political controversy between the British government, the Provisional Government of the Irish Free State and the government of Northern Ireland, and became the archetypal story of innocent Catholic lives taken by the intercommunal conflict in the six counties which became Northern Ireland in 1920‒22. This article seeks to contribute to the understanding of the role of this intercommunal conflict in Irish and British politics, using the Weaver Street bombing as a case study. This article analyses nationalist representation of the conflict as an orchestrated campaign against Catholics, ‘a pogrom’; unionist representation of the conflict as loyalist self-defence against the I.R.A.; and the British government's effort to publicly maintain neutrality in the conflict.
British Army intelligence in provincial Ireland, 1919‒1921: organisation, outcomes and the 6th Division blacklist
Authors: Bielenberg Andy , Borgonovo John
Published: February 2024

Intelligence played a critical role in the Irish War of Independence, though debate remains about the effectiveness of British information-gathering. Historians have focused largely on the intelligence war in Dublin. This article examines British Army intelligence in the 6th Division area (roughly the southern third of the island). It will contextualise British military intelligence before the conflict and traces the slow development of an intelligence organisation in the 6th Division. It then considers the sources and nature of British information gathering, particularly interrogation of prisoners and the collection and analysis of captured documents. Military intelligence summaries and a ‘Blacklist’ of I.R.A. suspects across the 6th Division are used to ascertain the quality of military intelligence products during the final stages of the conflict. The ‘Blacklist’ can be contrasted with I.R.A. unit arrest data and leadership lists, to assess the effectiveness of British military intelligence at a county level. This comparison provides a new measure of British performance, clearly revealing the limitations of British military intelligence in the 6th Division, particularly when compared to relatively more successful results achieved by crown forces in the Dublin District.
Response of the Central Pacific Intertropical Convergence Zone to Northern Hemisphere Cooling During the Last Glacial Maximum and Heinrich Stadial 1
Authors: Kim Mun Gi , Seo Inah , Hyeong Kiseong
Published: February 2024

The latitudinal position of the Intertropical Convergence Zone (ITCZ) reflects the energy imbalance between the hemispheres. Southward displacements of the ITCZ during the Last Glacial Maximum (LGM; 19–26.5 ka) and Heinrich Stadial 1 (HS1; 14.6–17.5 ka), are widely accepted, but their magnitude is controversial. Geochemistry of detrital fractions in down‐core sediments collected from 6°N to equator along the 131.5°W transect reveal a distinct shift in εNd, La/Yb, and La–Sc–Th composition from predominantly northern hemisphere‐sourced to mixed northern and southern hemisphere‐sourced signal at 3°N–4°N during the LGM and 3°N–6°N during HS1. These contrasting provenance signals point to the past ITCZ functioning as a dust barrier. Given that a comparable geochemical demarcation currently occurs at 6°N–7°N, our data suggest that the ITCZ migrated southward by ∼3° during the LGM and ∼1°–3° during HS1 relative to its modern position in the central Pacific.
Analysis of Beach Cusp Formation and Evolution Using High‐Frequency 3D Lidar Scans
Authors: O’Dea Annika , Brodie Katherine
Published: February 2024

In this study, beach cusp characteristics were explored using 15 months of 3D lidar scans collected hourly at the Field Research Facility in Duck, NC. Fourier analyses were performed on lidar‐derived beach elevation contours to generate spatial cusp spectra. Active cusp events were identified on the basis of the location and magnitude of each spectrum's peak and used to evaluate conditions during cusp formation and evolution. Cusps primarily developed during times with normally‐incident, long period, low energy wave conditions with low frequency spread, and reflective beach conditions. The upper and lower beaches often exhibited different behavior and morphologies, with persistent upper‐beach cusps lasting days to months and dynamic lower‐beach cusps evolving over individual tidal cycles. At times, beaches exhibiting multiple cusp systems reverted to a single cusp system extending over the entire beach when the high‐tide waterline reached the upper‐beach cusps, with the location and spacing of the resulting lower‐beach cusps controlled by the upper‐beach cusps. These observations are consistent with a “morphological coupling” hypothesis proposing that hydrodynamic‐morphodynamic feedbacks between the swash and upper‐beach cusps can result in the formation of lower‐beach cusps with a related wavelength as the tide falls. However, there were also times when the high‐tide waterline reached the upper‐beach cusps that did not result in a unified beach state. These results suggest that while morphological coupling is often an important factor in controlling the development of new lower‐beach cusps, this coupling cannot initiate cusp formation in hydrodynamic conditions outside those favorable for cusp activity.
Wearable respiratory sensors for health monitoring
Authors: Yin Zhifu , Yang Yang , Hu Cong , Li Jinzhe , Qin Boyu , Yang Xue
Published: February 2024

Real-time monitoring and early warning of human health conditions is an important function of wearable devices. Along with the development of the Internet of Things and the medical drive for early detection and treatment, wearable devices will become increasingly important in the future. Compared with traditional sensors, wearable sensors with mechanical softness and deformability are able to adapt to geometric nonlinearities and deformations caused by motion that occurs in application scenarios, thus ensuring stable and effective signal output under various complex working conditions. Various novel sensing materials have been developed for the detection of various biomarkers of respiration over the past few years. Here, we summarize the latest innovations in wearable respiratory sensors, highlighting the dominant sensing materials, designs, sensing mechanisms, and clinical implications. Finally, the future challenges and directions of wearable respiratory sensors are outlined toward promoting advancement in the field of wearable respiratory monitoring.
Grid-like entorhinal representation of an abstract value space during prospective decision making
Authors: Nitsch Alexander , Garvert Mona M. , Bellmund Jacob L. S. , Schuck Nicolas W. , Doeller Christian F.
Published: February 2024

How valuable a choice option is often changes over time, making the prediction of value changes an important challenge for decision making. Prior studies identified a cognitive map in the hippocampal-entorhinal system that encodes relationships between states and enables prediction of future states, but does not inherently convey value during prospective decision making. In this fMRI study, participants predicted changing values of choice options in a sequence, forming a trajectory through an abstract two-dimensional value space. During this task, the entorhinal cortex exhibited a grid-like representation with an orientation aligned to the axis through the value space most informative for choices. A network of brain regions, including ventromedial prefrontal cortex, tracked the prospective value difference between options. These findings suggest that the entorhinal grid system supports the prediction of future values by representing a cognitive map, which might be used to generate lower-dimensional value signals to guide prospective decision making.
An integrated self-optimizing programmable chemical synthesis and reaction engine
Authors: Leonov Artem I. , Hammer Alexander J. S. , Lach Slawomir , Mehr S. Hessam M. , Caramelli Dario , Angelone Davide , Khan Aamir , O’Sullivan Steven , Craven Matthew , Wilbraham Liam , Cronin Leroy
Published: February 2024

Robotic platforms for chemistry are developing rapidly but most systems are not currently able to adapt to changing circumstances in real-time. We present a dynamically programmable system capable of making, optimizing, and discovering new molecules which utilizes seven sensors that continuously monitor the reaction. By developing a dynamic programming language, we demonstrate the 10-fold scale-up of a highly exothermic oxidation reaction, end point detection, as well as detecting critical hardware failures. We also show how the use of in-line spectroscopy such as HPLC, Raman, and NMR can be used for closed-loop optimization of reactions, exemplified using Van Leusen oxazole synthesis, a four-component Ugi condensation and manganese-catalysed epoxidation reactions, as well as two previously unreported reactions, discovered from a selected chemical space, providing up to 50% yield improvement over 25–50 iterations. Finally, we demonstrate an experimental pipeline to explore a trifluoromethylations reaction space, that discovers new molecules.
Elemental partitioning-mediated crystalline-to-amorphous phase transformation under quasi-static deformation
Authors: Wu Ge , Liu Chang , Yan Yong-Qiang , Liu Sida , Ma Xinyu , Yue Shengying , Shan Zhi-Wei
Published: February 2024

The transformation induced plasticity phenomenon occurs when one phase transforms to another one during plastic deformation, which is usually diffusionless. Here we present elemental partitioning-mediated crystalline-to-amorphous phase transformation during quasi-static plastic deformation, in an alloy in form of a Cr-Ni-Co (crystalline)/Zr-Ti-Nb-Hf-Ni-Co (amorphous) nanolaminated composite, where the constitute elements of the two phases have large negative mixing enthalpy. Upon plastic deformation, atomic intermixing occurs between adjacent amorphous and crystalline phases due to extensive rearrangement of atoms at the interfaces. The large negative mixing enthalpy among the constituent elements promotes amorphous phase transformation of the original crystalline phase, which shows different composition and short-range-order structure compared with the other amorphous phase. The reduced size of the crystalline phase shortens mean-free-path of dislocations, facilitating strain hardening. The enthalpy-guided alloy design based on crystalline-to-amorphous phase transformation opens up an avenue for the development of crystal-glass composite alloys with ultrahigh strength and large plasticity.
Natural diversity screening, assay development, and characterization of nylon-6 enzymatic depolymerization
Authors: Bell Elizabeth L. , Rosetto Gloria , Ingraham Morgan A. , Ramirez Kelsey J. , Lincoln Clarissa , Clarke Ryan W. , Gado Japheth E. , Lilly Jacob L. , Kucharzyk Katarzyna H. , Erickson Erika , Beckham Gregg T.
Published: February 2024

Successes in biocatalytic polyester recycling have raised the possibility of deconstructing alternative polymers enzymatically, with polyamide (PA) being a logical target due to the array of amide-cleaving enzymes present in nature. Here, we screen 40 potential natural and engineered nylon-hydrolyzing enzymes (nylonases), using mass spectrometry to quantify eight compounds resulting from enzymatic nylon-6 (PA6) hydrolysis. Comparative time-course reactions incubated at 40-70 °C showcase enzyme-dependent variations in product distributions and extent of PA6 film depolymerization, with significant nylon deconstruction activity appearing rare. The most active nylonase, a NylCK variant we rationally thermostabilized (an N-terminal nucleophile (Ntn) hydrolase, NylCK-TS, Tm = 87.4 °C, 16.4 °C higher than the wild-type), hydrolyzes 0.67 wt% of a PA6 film. Reactions fail to restart after fresh enzyme addition, indicating that substrate-based limitations, such as restricted enzyme access to hydrolysable bonds, prohibit more extensive deconstruction. Overall, this study expands our understanding of nylonase activity distribution, indicates that Ntn hydrolases may have the greatest potential for further development, and identifies key targets for progressing PA6 enzymatic depolymerization, including improving enzyme activity, product selectivity, and enhancing polymer accessibility.
Exploring the future adult vaccine landscape—crowded schedules and new dynamics
Authors: Jones Charles H. , Jenkins Matthew P. , Adam Williams B. , Welch Verna L. , True Jane M.
Published: February 2024

Amidst the backdrop of the COVID-19 pandemic, vaccine innovation has garnered significant attention, but this field was already on the cusp of a groundbreaking renaissance. Propelling these advancements are scientific and technological breakthroughs, alongside a growing understanding of the societal and economic boons vaccines offer, particularly for non-pediatric populations like adults and the immunocompromised. In a departure from previous decades where vaccine launches could be seamlessly integrated into existing processes, we anticipate potentially than 100 novel, risk-adjusted product launches over the next 10 years in the adult vaccine market, primarily addressing new indications. However, this segment is infamous for its challenges: low uptake, funding shortfalls, and operational hurdles linked to delivery and administration. To unlock the societal benefits of this burgeoning expansion, we need to adopt a fresh perspective to steer through the dynamics sparked by the rapid growth of the global adult vaccine market. This article aims to provide that fresh perspective, offering a detailed analysis of the anticipated number of adult vaccine approvals by category and exploring how our understanding of barriers to adult vaccine uptake might evolve. We incorporated pertinent insights from external stakeholder interviews, spotlighting shifting preferences, perceptions, priorities, and decision-making criteria. Consequently, this article aspires to serve as a pivotal starting point for industry participants, equipping them with the knowledge to skillfully navigate the anticipated surge in both volume and complexity.
Silicon photonics-based high-energy passively Q-switched laser
Authors: Singh Neetesh , Lorenzen Jan , Sinobad Milan , Wang Kai , Liapis Andreas C. , Frankis Henry C. , Haugg Stefanie , Francis Henry , Carreira Jose , Geiselmann Michael , Gaafar Mahmoud A. , Herr Tobias , Bradley Jonathan D. B. , Sun Zhipei , Garcia-Blanco Sonia M. , Kärtner Franz X.
Published: February 2024

Chip-scale, high-energy optical pulse generation is becoming increasingly important as integrated optics expands into space and medical applications where miniaturization is needed. Q-switching of the laser cavity was historically the first technique to generate high-energy pulses, and typically such systems are in the realm of large bench-top solid-state lasers and fibre lasers, especially in the long wavelength range >1.8 µm, thanks to their large energy storage capacity. However, in integrated photonics, the very property of tight mode confinement that enables a small form factor becomes an impediment to high-energy applications owing to small optical mode cross-sections. Here we demonstrate a high-energy silicon photonics-based passively Q-switched laser with a compact footprint using a rare-earth gain-based large-mode-area waveguide. We demonstrate high on-chip output pulse energies of >150 nJ and 250 ns pulse duration in a single transverse fundamental mode in the retina-safe spectral region (1.9 µm), with a slope efficiency of ~40% in a footprint of ~9 mm2. The high-energy pulse generation demonstrated in this work is comparable to or in many cases exceeds that of Q-switched fibre lasers. This bodes well for field applications in medicine and space.
PLAS-20k: Extended Dataset of Protein-Ligand Affinities from MD Simulations for Machine Learning Applications
Authors: Korlepara Divya B. , C. S. Vasavi , Srivastava Rakesh , Pal Pradeep Kumar , Raza Saalim H. , Kumar Vishal , Pandit Shivam , Nair Aathira G. , Pandey Sanjana , Sharma Shubham , Jeurkar Shruti , Thakran Kavita , Jaglan Reena , Verma Shivangi , Ramachandran Indhu , Chatterjee Prathit , Nayar Divya , Priyakumar U. Deva
Published: February 2024

Computing binding affinities is of great importance in drug discovery pipeline and its prediction using advanced machine learning methods still remains a major challenge as the existing datasets and models do not consider the dynamic features of protein-ligand interactions. To this end, we have developed PLAS-20k dataset, an extension of previously developed PLAS-5k, with 97,500 independent simulations on a total of 19,500 different protein-ligand complexes. Our results show good correlation with the available experimental values, performing better than docking scores. This holds true even for a subset of ligands that follows Lipinski’s rule, and for diverse clusters of complex structures, thereby highlighting the importance of PLAS-20k dataset in developing new ML models. Along with this, our dataset is also beneficial in classifying strong and weak binders compared to docking. Further, OnionNet model has been retrained on PLAS-20k dataset and is provided as a baseline for the prediction of binding affinities. We believe that large-scale MD-based datasets along with trajectories will form new synergy, paving the way for accelerating drug discovery.
Tracking an untracked space debris after an inelastic collision using physics informed neural network
Authors: M Harsha , Singh Gurpreet , Kumar Vinod , Buduru Arun Balaji , Biswas Sanat K.
Published: February 2024

With the sustained rise in satellite deployment in Low Earth Orbits, the collision risk from untracked space debris is also increasing. Often small-sized space debris (below 10 cm) are hard to track using the existing state-of-the-art methods. However, knowing such space debris’ trajectory is crucial to avoid future collisions. We present a Physics Informed Neural Network (PINN)—based approach for estimation of the trajectory of space debris after a collision event between active satellite and space debris. In this work, we have simulated 8565 inelastic collision events between active satellites and space debris. To obtain the states of the active satellite, we use the TLE data of 1647 Starlink and 66 LEMUR satellites obtained from space-track.org. The velocity of space debris is initialized using our proposed velocity sampling method, and the coefficient of restitution is sampled from our proposed Gaussian mixture-based probability density function. Using the velocities of the colliding objects before the collision, we calculate the post-collision velocities and record the observations. The state (position and velocity), coefficient of restitution, and mass estimation of un-tracked space debris after an inelastic collision event along with the tracked active satellite can be posed as an optimization problem by observing the deviation of the active satellite from the trajectory. We have applied the classical optimization method, the Lagrange multiplier approach, for solving the above optimization problem and observed that its state estimation is not satisfactory as the system is under-determined. Subsequently, we have designed Deep Neural network-based methods and Physics Informed Neural Network (PINN) based methods for solving the above optimization problem. We have compared the performance of the models using root mean square error (RMSE) and interquartile range of the predictions. It has been observed that the PINN-based methods provide a better estimation performance for position, velocity, mass and coefficient of restitution of the space debris compared to other methods.
Gender differences in pain perception among burning mouth syndrome patients: a cross-sectional study of 242 men and 242 women
Authors: Calabria Elena , Canfora Federica , Leuci Stefania , Coppola Noemi , Pecoraro Giuseppe , Giudice Amerigo , Antonelli Alessandro , Aria Massimo , D’Aniello Luca , Mignogna Michele Davide , Adamo Daniela
Published: February 2024

Several orofacial painful conditions are influenced by gender-related factors, but no studies are available with regard to Burning Mouth Syndrome (BMS). The present study aimed at investigating gender differences among BMS patients and their influence on pain perception. 242 BMS males (BMSm) and 242 BMS females (BMSf) matched for age were consecutively enrolled. Sociodemographic and clinical characteristics were recorded and the numeric rating scale (NRS), the Total Pain Rating Index (T-PRI), the Hamilton rating scale for anxiety and depression (HAM-A, HAM-D), the Pittsburgh sleep quality index (PSQI) and the Epworth sleepiness scale (ESS) were administered. The BMSm presented statistically significant higher levels of education and rate of employment compared to the BMSf (p-values: 0.001**). Moreover, the BMSm were greater consumers of alcohol and had a higher BMI than the BMSf (p-values: < 0.001**, 0.034*). With respect to systemic comorbidities, cardiovascular diseases were statistically more prevalent among the BMSm, while hypothyroidism was more frequent in the BMSf (p-vales: < 0.001**). No differences were noted between the two groups in terms of oral symptoms and in the median scores of NRS, T-PRI, HAM-A, HAM-D, PSQI and ESS. Interestingly, the multivariate regression analysis revealed that, while anxiety, high BMI, poor sleep and high level of T-PRI were correlated to the intensity of pain (NRS) in both groups, low education was additional predictor of pain in BMSf. Further, depression, alcohol and intensity of pain were factors positively associated to the quality of pain (T-PRI) in the BMSm, whereas low education, non-married status and NRS were correlated to the T-PRI, in the BMSf. Surprisingly, smoking was inversely correlated to the intensity of pain and quality of pain respectively in BMSf and BMSm. Sociodemographic and risk factors were found to differently influence pain perception in BMSm and BMSf. Therefore, clinicians should take into account gender differences in the assessment of BMS patients to better tailor the overall pain management.
Henri Cochet's theory of angles in tennis (1933) reveals a new facet of anticipation
Authors: Benguigui Nicolas , Rioult François , Kauffmann François , Miller-Dicks Matt , Murphy Colm P.
Published: February 2024

In this study, we tested the theory of angles that was proposed almost a century ago by the tennis player Henri Cochet. This theory proposes that expert tennis players should position themselves on the bisector of the angle of the opponent’s possibilities in order to optimize shot return, suggesting a geometric occupation of the court relative to the opponent's affordances; namely what he/she is capable of doing. We tested this hypothesis by analysing player and ball positioning data from professional tennis matches recorded with a Hawk-Eye system. We compared this hypothesis with two alternative computational and probabilistic hypotheses which would consist in positioning oneself on the average or the median of the shots usually played from a given location. The results show that expert tennis players apply the principles of the theory of angles and thus confirm Henri Cochet's intuition. That is, for lateral court positioning, a geometric strategy is deemed optimal by expert players. It also appears that the more experienced the players are, the more precise their application of this strategy becomes.
Mesh-based GNN surrogates for time-independent PDEs
Authors: Gladstone Rini Jasmine , Rahmani Helia , Suryakumar Vishvas , Meidani Hadi , D’Elia Marta , Zareei Ahmad
Published: February 2024

Physics-based deep learning frameworks have shown to be effective in accurately modeling the dynamics of complex physical systems with generalization capability across problem inputs. However, time-independent problems pose the challenge of requiring long-range exchange of information across the computational domain for obtaining accurate predictions. In the context of graph neural networks (GNNs), this calls for deeper networks, which, in turn, may compromise or slow down the training process. In this work, we present two GNN architectures to overcome this challenge—the edge augmented GNN and the multi-GNN. We show that both these networks perform significantly better than baseline methods, such as MeshGraphNets, when applied to time-independent solid mechanics problems. Furthermore, the proposed architectures generalize well to unseen domains, boundary conditions, and materials. Here, the treatment of variable domains is facilitated by a novel coordinate transformation that enables rotation and translation invariance. By broadening the range of problems that neural operators based on graph neural networks can tackle, this paper provides the groundwork for their application to complex scientific and industrial settings.
Effects of exercise-based interventions on gluteal tendinopathy. Systematic review with meta-analysis
Authors: Patricio Cordeiro Thaisy Thuany , Rocha Emannuel Alcides Bezerra , Scattone Silva Rodrigo
Published: February 2024

The objective of this review was to evaluate the effect of exercise on pain intensity, function, and quality of life in individuals with gluteal tendinopathy. Searches were carried out in PUBMED, EMBASE, CINAHL, Cochrane Library, and PEDro databases. Randomized or quasi-randomized controlled trials were included. Five studies met the eligibility criteria, comparing exercise-based interventions with minimal interventions and/or corticosteroid injections. Three studies, involving 383 participants, were included in the quantitative analysis. Meta-analyses showed that exercise is superior to minimal intervention for function in short-term [mean difference (MD) = 10.24; 95% confidence interval (95%CI) = 5.98, 14.50) and long-term (MD = 6.54; 95%CI = 1.88, 11.21]). However, no difference was observed for quality of life in the short [standardized mean difference (SMD) = 0.33; 95%CI = −0.29, 0.94] and long-term (SMD = 0.11; 95%CI = −0.16, 0.37). The effect of exercise was no different from that of corticosteroid injections for pain intensity in the short (MD = 1.25; 95%CI = −3.56, 6.05) and long-term (MD = −1.37; 95%CI = −3.72, 0.98]). In conclusion, exercise is superior to minimal interventions for function in the short- and long-term in individuals with gluteal tendinopathy. Exercise and corticosteroid injections had similar effects on pain intensity, however, exercise showed a higher treatment success rate when compared to corticosteroid injections in this population. The GRADE analysis revealed that the certainty of the evidence ranges from low to very low, therefore, large high-quality randomized controlled trials are recommended.

PROSPERO registration number: CRD42021242853.
Mobile app activity engagement by cancer patients and their caregivers informs remote monitoring
Authors: Yunis Reem , Fonda Stephanie J. , Aghaee Sara , Kubo Ai , Davis Sharon W. , Liu Raymond , Neeman Elad , Oakley-Girvan Ingrid
Published: February 2024

Mobile phone applications (“apps”) are potentially an effective, low-burden method to collect patient-reported outcomes outside the clinical setting. Using such apps consistently and in a timely way is critical for complete and accurate data capture, but no studies of concurrent reporting by cancer patient–caregiver dyads have been published in the peer-reviewed literature. This study assessed app engagement, defined as adherence, timing, and attrition with two smartphone applications, one for adult cancer patients and one for their informal caregivers. This was a single-arm, pilot study in which adult cancer patients undergoing IV chemotherapy or immunotherapy used the DigiBioMarC app, and their caregivers used the TOGETHERCare app, for approximately one month to report weekly on the patients’ symptoms and wellbeing. Using app timestamp metadata, we assessed user adherence, overall and by participant characteristics. Fifty patient–caregiver dyads completed the study. Within the one-month study period, both adult cancer patients and their informal caregivers were highly adherent, with app activity completion at 86% for cancer patients and 84% for caregivers. Caregivers completed 86% of symptom reports, while cancer patients completed 89% of symptom reports. Cancer patients and their caregivers completed most activities within 48 h of availability on the app. These results suggest that the DigiBioMarC and TOGETHERCare apps can be used to collect patient- and caregiver-reported outcomes data during intensive treatment. From our research, we conclude that metadata from mobile apps can be used to inform clinical teams about study participants' engagement and wellbeing outside the clinical setting.