bluuebunny/crossref_metadata_2025 huggingface dataset:
A Framework for the Use and Likelihood of Regulatory Acceptance of Single-Arm Trials
Authors: Subramaniam Disha , Anderson-Smits Colin , Rubinstein Rebecca , Thai Sydney T. , Purcell Rose , Girman Cynthia
Published: September 2024

Background

Single-arm clinical trials (SAT) are common in drug and biologic submissions for rare or life-threatening conditions, especially when no therapeutic options exist. External control arms (ECAs) improve interpretation of SATs but pose methodological and regulatory challenges.

Objective

Through narrative reviews and expert input, we developed a framework for considerations that might influence regulatory use and likelihood of regulatory acceptance of an SAT, identifying non-oncology first indication approvals as an area of interest. We systematically analyzed FDA and EMA approvals using SATs as pivotal evidence. The framework guided outcome abstraction on regulatory responses.

Methods

We examined all non-oncology FDA and EMA drug and biologic approvals for first indications from 2019 to 2022 to identify those with SAT as pivotal safety or efficacy evidence. We abstracted outcomes, key study design features, regulator responses to SAT and (where applicable) ECA design, and product label content.

Results

Among 20 SAT-based FDA approvals and 17 SAT-based EMA approvals, most common indications were progressive rare diseases with high unmet need/limited therapeutic options and a natural history without spontaneous improvement. Of the types of comparators, most were natural history cohorts (45% FDA; 47% EMA) and baseline controls (40% FDA; 47% EMA). Common critiques were of non-contemporaneous ECAs, subjective endpoints, and baseline covariate imbalance between arms.

Conclusion

Based on recent FDA and EMA approvals, the likelihood of regulatory success for SATs with ECAs depends on many design, analytic, and data quality considerations. Our framework is useful in early drug development when considering SAT strategies for evidence generation.
Latest Developments in “Adaptive Enrichment” Clinical Trial Designs in Oncology
Authors: Tu Yue , Renfro Lindsay A.
Published: September 2024

As cancer has become better understood on the molecular level with the evolution of gene sequencing techniques, considerations for individualized therapy using predictive biomarkers (those associated with a treatment’s effect) have shifted to a new level. In the last decade or so, randomized “adaptive enrichment” clinical trials have become increasingly utilized to strike a balance between enrolling all patients with a given tumor type, versus enrolling only a subpopulation whose tumors are defined by a potential predictive biomarker related to the mechanism of action of the experimental therapy. In this review article, we review recent innovative design extensions and adaptations to adaptive enrichment designs proposed during the last few years in the clinical trial methodology literature, both from Bayesian and frequentist perspectives.
Frege and the Fundamental Abstraction
Authors: Hutchinson Jim
Published: September 2024

According to Charles Travis, Frege’s principle to “always to sharply separate the psychological from the logical, the subjective from the objective” involves a move called “the fundamental abstraction.” I try to explain what this abstraction is and why it is interesting. I then raise a problem for it, and describe what I think is a better way to understand Frege’s principle.
Mixture theory for diffuse interface models of two-phase flows
Authors: Abels Helmut
Published: September 2024

Diffuse interface models are an important class of models used to describe multi-phase flows. In the case of incompressible viscous fluids there are a number of different diffuse interface models which have been known for many years. Nevertheless, a model based on mixture theory with a full set of conservation laws for the conservation of linear momentum of each constituent was not yet available. This gap was filled by ten Eikelder et al. (J. Fluid Mech., in press) recently and a first comparison with known models of Navier–Stokes/Cahn–Hilliard type is given. A detailed understanding of the relations between these models remains an important question.
Treating with minerals in the Middle Ages: the rare substance mūmiyāʾ (pitch-asphalt) and its medicinal uses in Byzantium
Authors: Bouras-Vallianatos Petros , Käs Fabian
Published: September 2024

Premodern medicine used a variety of mineral substances for therapeutic purposes. The present article deals with pitch-asphalt, and, in particular, a precious kind of it called mūmiyāʾ originating in Persia. It was first described in detail in the Arabic pharmacological tradition, and its fame spread throughout the medieval Mediterranean, including Byzantium. By editing and examining for the first time a previously unexplored medieval Greek text on mūmiyāʾ, this study offers new insights into the medicinal uses of this substance. It also significantly increases our understanding of the intense cross-cultural transfer of medical knowledge from the Islamicate world to Byzantium by showing that this was not merely based on the translation of a few Arabic medical works into Greek, but was a multifaceted phenomenon involving a complex nexus of sources that require further investigation.
Are pro-immigrant messages ineffective? Moralization as a rhetorical strategy for mainstream parties
Authors: Simonsen Kristina Bakkær
Published: September 2024

This study contributes to understanding mainstream parties' room for maneuver in the immigration domain by exploring the impact of moralization as a rhetorical strategy. Research has found anti-immigrant messages to be more effective than pro-immigrant messages in shaping public opinion. However, a pre-registered survey experiment with Danish respondents reveals that moral rhetoric enhances policy support for pro-immigrant communication, rendering it as effective as anti-immigrant messages. Partisan-motivated reasoning influences reactions to all messages except the non-moral anti-immigrant message, suggesting that when appealing to out-party supporters, mainstream parties still meet least resistance with an exclusive platform.
ON A PROBLEM OF PONGSRIIAM ON THE SUM OF DIVISORS
Authors: WANG RUI-JING
Published: September 2024

For any positive integer n, let
$\sigma (n)$
be the sum of all positive divisors of n. We prove that for every integer k with
$1\leq k\leq 29$
and
$(k,30)=1,$

$$ \begin{align*} \sum_{n\leq K}\sigma(30n)>\sum_{n\leq K}\sigma(30n+k) \end{align*} $$

for all
$K\in \mathbb {N},$
which gives a positive answer to a problem posed by Pongsriiam [‘Sums of divisors on arithmetic progressions’, Period. Math. Hungar. 88 (2024), 443–460].
Hours With St Jerome
Authors: Pope Hugh
Published: September 2024

Though perhaps most people who are at all familiar with them appreciate
the writings of St Augustine, comparatively few feel any attraction for
those of St Jerome who, unlike St Augustine, has left us no sermons or
devotional treatises, his work consisting for the most part of technical
Commentaries and minute disquisitions on difficult passages of Holy
Scripture.

Both Saints have left us a vast correspondence. But how their letters
differ! If we except Augustine’s earlier ones, his philosophical discussions
during his first days as a Christian, the remainder are for the most part
the outpourings of a shepherd of souls; the same is true of his sermons
which lend themselves to quotation at every turn and wherein the devout can
always find food for their souls. St Jerome, too, has left us many spiritual
letters. But we get the impression that such letters were not his life’s
work; he writes them almost under protest as though feeling that they are
stealing time from the real work to which God has called him, that of
translating and commenting on the Bible.
The Mystery And ‘The Mysteries'
Authors: Albert S. M.
Published: September 2024

As October, the month of the Rosary, is here, our thoughts may well turn to the consideration of the position of our Blessed Lady in the life of the Church as a whole and in our own. In some minds this consideration arouses misgivings. Does the trend of modern Mariology tend to give her an exaggerated prominence, they ask? This fear is almost as old as heresy, yet it troubles even devout Catholics today. Are popular forms of devotion to our Lady such as the Family Rosary, Perpetual Novenas, the Fatima cultus, being used as escapes from the basic obligations of religion, leading away from God and not to him? Does the widespread de Montfort consecration with its stress on ‘All through Mary’ conflict with a spirituality which seeks to centre everything on the Mass? Isn't the use of the Rosary at Mass an obstacle to the spread of the liturgical spint through a wider use of the Missal? Queries such as these may be only academic difficulties of the theorists.
Who Art In Heaven
Authors: Steuart R. H. J.
Published: September 2024

‘Who art in Heaven.’ This is a puzzling expres- sion. Where is Heaven, and how can God be fixed in Heaven or anywhere at all? In old days people really did think that there was a hard-and-fast place in the universe above us. They thought that the sky was a solid dome, a firmament, and that there was water above and below, and that the water poised above the dome of the sky was allowed to descend. They used the expressions of their day. It is the natural instinct in man to look up to God as if he were poised actually, physically above us.

When we talk of Heaven, the Church does not mean us to believe that God is enthroned in one particular place above. God is everywhere in a sense that cannot be described in terms of our experience.
The Return Of Symbols
Authors: Nicholl Donald
Published: September 2024

Those chosen to judge the ‘Political Prisoner’ competition in London disagreed about the respective merits of the different entries. But on one point they were unanimous: that merely factual models (of prisoners looking out from behind barbed wire, for instance) are quite inadequate; and that only something symbolic is capable of re-Presenting the reality of the political prisoner situation. Their insistence that it requires a symbol, not a mere photographic reproduction or sign, to re-present reality is but one example of that search for adequate sym- bols in which the most sensitive minds of our times are engaged. The number of those engaged in this search, and the intensity of their efforts, is easily under-estimated because the persons concerned do not fall into the customary political, religious or artistic categories; and so one fails to observe what they have in common until one becomes aware oneself of the search that is on.
Beginning To Know Saint Bernard
Authors: Morson John
Published: September 2024

The English Cistercians recently acquired a manuscript, copied in about 1200, of the first Life of St Bernard. It is a good specimen of the way in which the Life was distributed through the Cistercian and other monateries of Europe in the decades following the saint's death and also shows the kind of difficulty which a small or newly-founded house may have had in setting up and mainlining taining its scriptorium. The codex is all the more valuable because it is headed by a miniature portrait of the saint executed probably when many who had seen him were still alive. The portrait from the first folio of the codex is repro- duced, a little larger than actual size, in this issue. If any are Interested in a more technical account of the MS.
A Forerunner Of St John Of The Gross
Authors: D.A.B.
Published: September 2024

The Golden Age of Spanish Spiritual Theology flowered suddenly, almost as though a summer were to burst upon us without a springtide. Not that Spaniards were ignorant of the subject, either in theory or in practice, but previous to the middle of the fifteenth century tury produced scarcely any native writers. The medieval period proper was one of importation and imitation. Works of foreign authorship were translated, and Spain was long content to draw upon the common heritage of Western Christendom, for her mystical as for her dogmatic theology. Then, roughly half-way through the century, there begins a long line of Spanish writers who have assimilated the masterpieces of other lands, whether in the original or in translation, and are becoming increasingly original until we reach peak point with St Teresa and St John of the Cross.
The ‘Our Father’ Considered: Part II: Commentary
Authors: Cyprian St , Devas Dominic
Published: September 2024

(viii) Our Father, Who Art In Heaven : At the very outset our Lord, whose teaching on concord and unity is habitually emphatic, shows that he does not mean us to pray as isolated individuals, everyone busy about his own affairs alone. We are not to my ‘My Father, in heaven’ or ‘Give me daily bread'. We are not to pray forgiveness only for our own sins, nor seek merely personal deliverance from temptation or immunity from harm. Our prayer is to be comprehensive, for all. We are to pray for the whole body of the faithful and not for one alone; or, better still, to see each individual as really and inseparably one with the whole body which we are. Each is to pray for all as constituting one single whole. That is what God wants: he is the God of peace: as Teacher his theme was peace and unity; as Redeemer he gathered the whole of humanity as one man to his embrace.
Padre Pio Da Pietrelcina
Authors: Hollings Michael
Published: September 2024

Padre Pio da Pietrelcina is not widely known, in England, and the occasional references to him give the wrong emphasis. If he is mentioned, it is usually as ‘that supposed stigmatist somewhere in Italy'; so that the immediate impression is adverse, even damning. Now that is as it should be. The masters of the spiritual life cry out to us: Beware of hysteria! Avoid strange phenomena! Live by Faith!

Early in the morning, before five, the sacristy door at St Giovanni Rotondo, near Foggia, opens and Padre Pio comes in to say Mass. He comes in slowly, almost shuffling. A tired face, the beard tinged with grey; a large nose, slightly splayed-out from suuff-taking; eyes that pierce and laugh, while the mouth and cheeks follow the eyes; a face serene, radiant, simple. Quite stout, quite short—you see such figures every day on the roads of Italian towns and countryside—the Cappucini.
The Apostolate To The Community
Authors: Davis H. F.
Published: September 2024

Is it the mission of Christianity only to save the souls of those whom we can persuade to come to church, or is it equally part of our mission to Christianise society? Father Michonneau and his collaborators in the parish of St Colombes in Paris have long been convinced that too exclusive a concentration on the first of these tasks is responsible for the relative failure of the Church among the industrial masses of the continent. In his parish, a few years ago, not more than five per cent of the total population could be regarded as practising Catholics. His book is an impassioned plea, fully supported by the late Cardinal suhard and blessed by Archbishop Cushrng of Boston, for the adoption of more realistic methods in dealing with such a situation. To begin with, they were convinced they had no right to spend all their time attending to the needs of the five per cent who were faithful, and forgetting the ninety-five per cent who were growing up with little knowledge of Christ and no knowledge of the Church.
A knowledge transfer method for human-robot collaborative disassembly of end-of-life power batteries based on augmented reality
Authors: Li Jie , Duan Liangliang , Qu Weibin , Zheng Hangbin
Published: September 2024

The disassembly of power batteries poses significant challenges due to their complex sources, diverse types, variations in design and manufacturing processes, and diverse service conditions. Human memory capacity and robot cognitive and understanding capabilities are limited when faced with different dismantling tasks for end-of-life power batteries. Insufficient human-computer interaction capabilities greatly hinder the efficiency of human-robot collaboration (HRC) operations. The existing HRC relies heavily on the experience of operators, while the existing disassembly system fails to update new disassembly strategies in real time when facing new battery varieties. Therefore, this paper proposes an augmented reality-assisted human-robot collaboration (AR-HRC) power battery dismantling system based on transfer learning. It consists of three modules: AR-HRC knowledge modeling, dismantling subgraph similarity assessment, and strategy transfer update. The AR-HRC knowledge modeling module aims to establish an intelligent mapping from tasks to collaborative strategies based on part features. Based on the evaluation of task similarity, the mobility assessment model divides subtasks into similar and dissimilar classes. For similar subtasks, the original dismantling strategy can be applied to the current task. However, for different subtasks, operators can issue instructions to the AR-HRC system through the human-computer interaction function of AR and develop new collaborative strategies based on actual conditions. Finally, a case study of power battery dismantling is conducted, and the results show that compared to traditional pre-programmed assembly, this system can improve dismantling efficiency and reduce cognitive burden.
Medication management and electrocardiogram screening in children with attention deficit hyperactivity disorder
Authors: Pentony Michaela , Ali Zainab , Moore Kieran , McNicholas Fiona , James Adam
Published: September 2024

Background:

To quantify the proportion of referrals sent to Crumlin Cardiology Department for cardiac screening prior to commencement or modifying attention deficit hyperactivity disorder medication and assess the number detected with a clinically significant abnormality.

Methods:

A prospective audit was performed over a 6-month period, from November 2021 to April 2022 inclusive. Referrals sent via outpatient department triage letters, electrocardiogram dept. email, and walk-in electrocardiogram service were screened for those pertaining to commencing or modifying medication for children with attention deficit hyperactivity disorder. Each referral was coded against National Institute for Health and Care Excellence guidelines to determine the degree of clinical details given. Reported abnormalities, recommended management, and correspondence were recorded.

Results:

Ninety-one referrals were received during the 6-month audit period. More than half lacked a clinical indication for referral (53/91, 58.2%), with fewer than one third (26/91, 28.5%) meeting National Institute for Health and Care Excellence criteria for referral for cardiology. Eighty (80/91) referrals had clinical outcomes available for review (missing outpatient department information and age outside of service range accounted for eleven referrals with unavailable clinical outcomes). Of the eighty clinically reviewed referrals, seventy-two (72/80, 90%) were reported as normal with no cardiology follow up required. Eight referrals (8/80, 10%) were reviewed in the Cardiology Outpatient Department prior to commencement or modifying attention deficit hyperactivity disorder medication. Of these, only one (1/80 1%) had a clinically significant abnormality which was a potential contraindication to attention deficit hyperactivity disorder medication use, and this referral was appropriate as per National Institute for Health and Care Excellence guidelines.

Conclusion:

Routine screening prior to attention deficit hyperactivity disorder medication prescription in the absence of clinical indications (as per National Institute for Health and Care Excellence) contributed to delays in medication initiation among young people with attention deficit hyperactivity disorder. Unnecessary referrals have resource implications for cardiology clinical team. Improved adherence to National Institute for Health and Care Excellence guidelines would provide benefits for patients and clinicians.
Food poverty among children aged 6–59 months in Brazil: results from the Brazilian National Survey on Child Nutrition (ENANI-2019)
Authors: Carneiro Letícia Barroso Vertulli , Lacerda Elisa Maria de Aquino , Oliveira Natália , Schincaglia Raquel Machado , Alves-Santos Nadya Helena , Berti Talita Lelis , Crispim Sandra Patricia , Farias Dayana Rodrigues , Mello Juliana Vieira de Castro , Normando Paula , Castro Inês Rugani Ribeiro , Kac Gilberto
Published: September 2024

Objective:

To describe the prevalence of food poverty according to dimensions of socio-economic inequality and the food groups consumed by Brazilian children.

Design:

Dietary data from a structured qualitative questionnaire collected by the Brazilian National Survey on Child Nutrition (ENANI-2019) were used. The new UNICEF indicator classified children who consumed 3–4 and <3 out of the eight food groups as living in moderate and severe food poverty, respectively. The prevalence of consumption of each food group and ultra-processed foods (UPF) was estimated by level of food poverty according to age categories (6–23; 24–59 months). The most frequent combinations of food groups consumed by children living in severe food poverty were calculated. Prevalence of levels of food poverty were explored according to socio-economic variables.

Setting:

123 municipalities of the five Brazilian macro-regions.

Participants:

12 582 children aged 6–59 months.

Results:

The prevalence of moderate and severe food poverty was 32·5 % (95 % CI 30·1, 34·9) and 6·0 % (95 % CI 5·0, 6·9), respectively. Children whose mother/caregiver had lower education (<8 years) and income levels (per capita minimum wage <¼) had the highest severe food poverty prevalence of 8·3 % (95 % CI 6·2, 10·4) and 7·5 % (95 % CI 5·6, 9·4), respectively. The most consumed food groups among children living in food poverty in all age categories were ‘dairy products’, ‘grains, roots, tubers, and plantains’ and ‘ultra-processed foods’.

Conclusion:

Food poverty prevalence was high among Brazilian children. A significant occurrence of milk consumption associated with grains and a considerable prevalence of UPF consumption were found among those living in severe food poverty.
An Instrument Error Budget for Space‐Based Absolute Flux Measurements of the Sky Synchrotron Spectrum Below 20 MHz
Authors: Rolla J. , Romero‐Wolf A. , Lazio T. J. W.
Published: September 2024

This work describes the instrumental error budget for space‐based measurements of the absolute flux of the sky synchrotron spectrum at frequencies below the ionospheric cutoff (20 MHz). We focus on an architecture using electrically short dipoles onboard a small satellite. The error budget combines the contributions of the dipole dimensions, plasma noise, stray capacitance, and front‐end amplifier input impedance. We treat the errors using both a Monte Carlo error propagation model and an analytical method. This error budget can be applied to a variety of experiments and used to ultimately improve the sensing capabilities of space‐based electrically short dipole instruments. The impact of individual uncertainty components, particularly stray capacitance, is explored in more detail.
The Role of the Polar Vortex Jet for Secondary and Higher‐Order Gravity Waves in the Northern Mesosphere and Thermosphere During 11–14 January 2016
Authors: Vadas Sharon L. , Becker Erich , Bossert Katrina , Hozumi Yuta , Stober Gunter , Harvey V. Lynn , Baumgarten Gerd , Hoffmann Lars
Published: September 2024

We analyze the gravity waves (GWs) from the ground to the thermosphere during 11–14 January 2016 using the nudged HI Altitude Mechanistic general Circulation Model. We find that the entrance, core and exit regions of the polar vortex jet are important for generating primary GWs and amplifying GWs from below. These primary GWs dissipate in the upper stratosphere/lower mesosphere and deposit momentum there; the atmosphere responds by generating secondary GWs. This process is repeated, resulting in medium to large‐scale higher‐order, thermospheric GWs. We find that the amplitudes of the secondary/higher‐order GWs from sources below the polar vortex jet are exponentially magnified. The higher‐order, thermospheric GWs have concentric ring, arc‐like and planar structures, and spread out latitudinally to 10 − 90°N. Those GWs with the largest amplitudes propagate against the background wind. Some of the higher‐order GWs generated over Europe propagate over the Arctic region then southward over the US to ∼15–20°N daily at ∼14 − 24 UT (∼9 − 16 LT) due to the favorable background wind. These GWs have horizontal wavelengths λH ∼ 200 − 2,200 km, horizontal phase speeds cH ∼ 165 − 260 m/s, and periods τr ∼ 0.3 − 2.4 hr. Such GWs could be misidentified as being generated by auroral activity. The large‐scale, higher‐order GWs are generated in the lower thermosphere and propagate southwestward daily across the northern mid‐thermosphere at ∼8–16 LT with λH ∼ 3,000 km and cH ∼ 650 m/s. We compare the simulated GWs with those observed by AIRS, VIIRS/DNB, lidar and meteor radars and find reasonable to good agreement. Thus the polar vortex jet is important for facilitating the global generation of medium to large‐scale, higher‐order thermospheric GWs via multi‐step vertical coupling.
PET imaging in rat brain shows opposite effects of acute and chronic alcohol exposure on phosphodiesterase-4B, an indirect biomarker of cAMP activity
Authors: Tang Shiyu , Kim Sung Won , Olsen-Dufour Amanda , Pearson Torben , Freaney Michael , Singley Erick , Jenkins Madeline , Burkard Nathaniel J. , Wozniak Aaron , Parcon Paul , Wu Shawn , Morse Cheryl L. , Jana Susovan , Liow Jeih-San , Zoghbi Sami S. , Vendruscolo Janaina C. M. , Vendruscolo Leandro F. , Pike Victor W. , Koob George F. , Volkow Nora D. , Innis Robert B.
Published: September 2024

The cyclic adenosine monophosphate (cAMP) cascade is thought to play an important role in regulating alcohol-dependent behaviors, with potentially opposite effects following acute versus chronic administration. Phosphodiesterase 4 (PDE4) is the primary brain enzyme that metabolizes cAMP, thereby terminating its signal. Radioligand binding to PDE4 serves as an indirect biomarker of cAMP activity, as cAMP-protein kinase A (PKA)-mediated phosphorylation of PDE4 increases its affinity for radioligand binding ~10-fold. Of the four PDE4 subtypes, PDE4B polymorphisms are known to be strongly associated with alcohol and substance use disorders. This study imaged rats with the PDE4B-preferring positron emission tomography (PET) radioligand [18F]PF-06445974 following acute and chronic ethanol administration, aiming to explore the potential of PDE4B PET imaging for future human studies. Compared to the control group treated with saline, acute alcohol administration (i.p. ethanol 0.5 g/kg) significantly increased whole brain uptake of [18F]PF-06445974 as early as 30 minutes post-exposure. This effect persisted at 2 hours, peaked at 4 hours, and diminished at 6 hours and 24 hours post-exposure. In contrast, in a rat model of alcohol dependence, [18F]PF-06445974 brain uptake was significantly reduced at 5 hours post-exposure and was normalized by 3 days. This reduction may reflect long-term adaptation to repeated alcohol-induced activation of cAMP signaling with chronic exposure. Taken together, the results suggest that PET imaging of PDE4B in individuals with alcohol use disorder (AUD) should be considered in conjunction with ongoing trials of PDE4 inhibitors to treat alcohol withdrawal and reduce alcohol consumption.
P-tau217 and other blood biomarkers of dementia: variation with time of day
Authors: della Monica Ciro , Revell Victoria , Atzori Giuseppe , Laban Rhiannon , Skene Simon S. , Heslegrave Amanda , Hassanin Hana , Nilforooshan Ramin , Zetterberg Henrik , Dijk Derk-Jan
Published: September 2024

Plasma biomarkers of dementia, including phosphorylated tau (p-tau217), offer promise as tools for diagnosis, stratification for clinical trials, monitoring disease progression, and assessing the success of interventions in those living with Alzheimer’s disease. However, currently, it is unknown whether these dementia biomarker levels vary with the time of day, which could have implications for their clinical value. In two protocols, we studied 38 participants (70.8 ± 7.6 years; mean ± SD) in a 27-h laboratory protocol with either two samples taken 12 h apart or 3-hourly blood sampling for 24 h in the presence of a sleep–wake cycle. The study population comprised people living with mild Alzheimer’s disease (PLWA, n = 8), partners/caregivers of PLWA (n = 6) and cognitively intact older adults (n = 24). Single-molecule array technology was used to measure phosphorylated tau (p-tau217) (ALZpath), amyloid-beta 40 (Aβ40), amyloid-beta 42 (Aβ42), glial fibrillary acidic protein, and neurofilament light (NfL) (Neuro 4-Plex E). Analysis with a linear mixed model (SAS, PROC MIXED) revealed a significant effect of time of day for p-tau217, Aβ40, Aβ42, and NfL, and a significant effect of participant group for p-tau217. For p-tau217, the lowest levels were observed in the morning upon waking and the highest values in the afternoon/early evening. The magnitude of the diurnal variation for p-tau217 was similar to the reported increase in p-tau217 over one year in amyloid-β-positive mild cognitively impaired people. Currently, the factors driving this diurnal variation are unknown and could be related to sleep, circadian mechanisms, activity, posture, or meals. Overall, this work implies that the time of day of sample collection may be relevant in the implementation and interpretation of plasma biomarkers in dementia research and care.
Polarization-entangled photons from a whispering gallery resonator
Authors: Huang Sheng-Hsuan , Dirmeier Thomas , Shafiee Golnoush , Laiho Kaisa , Strekalov Dmitry V. , Leuchs Gerd , Marquardt Christoph
Published: September 2024

Crystalline whispering gallery mode resonators (WGMRs) have been shown to facilitate versatile sources of quantum states that can efficiently interact with atomic systems. These features make WGMRs an efficient platform for quantum information processing. Here, we experimentally show that it is possible to generate polarization entanglement from WGMRs by using an interferometric scheme. Our scheme gives us the flexibility to control the phase of the generated entangled state by changing the relative phase of the interferometer. The S value of Clauser–Horne–Shimony–Holt’s inequality in the system is 2.45 ± 0.07, which violates the inequality by more than six standard deviations.
A randomised crossover trial of nitrate and breakfast on prefrontal cognitive and haemodynamic response functions
Authors: Heiland Emerald G. , Lindh Frida , Regan Callum , Ekblom Örjan , Kjellenberg Karin , Larsen Filip J. , Fernström Maria , Nyberg Gisela , Ekblom Maria M. , Helgadóttir Björg
Published: September 2024

It remains unknown whether dietary nitrate and breakfast may enhance working memory (WM) performance by augmenting physiological mechanisms and subjective psychological well-being. We performed a 3-arm randomised within-subject crossover study, with pretest-posttest comparisons, to test whether nitrate consumption via breakfast with a beetroot juice shot or regular breakfast compared to no breakfast improved WM (measured with n-back tests) and cognitive task-related changes in prefrontal cortical haemodynamic response (oxygenated- and deoxygenated-haemoglobin derived from functional near-infrared spectroscopy). In addition, effects on peripheral vascular function and self-reported psychological factors were assessed. In 60 adolescents (13–15 years old; 66% girls), WM improved in all conditions, with no intervention effects. Intervention effects were seen for oxygenated-haemoglobin changes, such that it increased after the breakfast with a nitrate shot during the WM tests and decreased after the regular breakfast. Thus, different neurophysiological mechanisms may be at play to preserve WM in adolescents depending on their breakfast composition. The trial was registered in the ISRCTN registry (ISRCTN16596056) on 21/02/2022.
Label-free assessment of complement-dependent cytotoxicity of therapeutic antibodies via a whole-cell MALDI mass spectrometry bioassay
Authors: Schmidt Stefan , Geisel Alexander , Enzlein Thomas , Fröhlich Björn C. , Pritchett Louise , Verneret Melanie , Graf Christian , Hopf Carsten
Published: September 2024

Potency assessment of monoclonal antibodies or corresponding biosimilars in cell-based assays is an essential prerequisite in biopharmaceutical research and development. However, cellular bioassays are still subject to limitations in sample throughput, speed, and often need costly reagents or labels as they are based on an indirect readout by luminescence or fluorescence. In contrast, whole-cell Matrix-Assisted Laser Desorption/Ionization Time-of-Flight (MALDI-TOF) Mass Spectrometry (MS) has emerged as a direct, fast and label-free technology for functional drug screening being able to unravel the molecular complexity of cellular response to pharmaceutical reagents. However, this approach has not yet been used for cellular testing of biologicals. In this study, we have conceived, developed and benchmarked a label-free MALDI-MS based cell bioassay workflow for the functional assessment of complement-dependent cytotoxicity (CDC) of Rituximab antibody. By computational evaluation of response profiles followed by subsequent m/z feature annotation via fragmentation analysis and trapped ion mobility MS, we identified adenosine triphosphate and glutathione as readily MS-assessable metabolite markers for CDC and demonstrate that robust concentration–response characteristics can be obtained by MALDI-TOF MS. Statistical assay performance indicators suggest that whole-cell MALDI-TOF MS could complement the toolbox for functional cellular testing of biopharmaceuticals.
Estimation of the crop evapotranspiration for Udham Singh Nagar district using modified Priestley-Taylor model and Landsat imagery
Authors: Satpathi Anurag , Danodia Abhishek , Abed Salwan Ali , Nain Ajeet Singh , Al-Ansari Nadhir , Ranjan Rajeev , Vishwakarma Dinesh Kumar , Gacem Amel , Mansour Lamjed , Yadav Krishna Kumar
Published: September 2024

The main challenges for utilizing daily evapotranspiration (ET) estimation in the study area revolve around the need for accurate and reliable data inputs, as well as the interpretation of ET dynamics within the context of local agricultural practices and environmental conditions. Factors such as cloud cover, atmospheric aerosols, and variations in land cover pose challenges to the precise estimation of ET from remote sensing data. This research aimed to utilize Landsat 8 and 9 datasets from the 2022–23 period in the Udham Singh Nagar district to apply the modified Priestley-Taylor (MPT) model for estimating ET. An average ET was estimated 1.33, 1.57, 1.70, 2.99, and 3.20 mm day−1 with 0.29, 0.33, 0.41, 0.69, and 1.03 standard deviation for December, January, February, March, and April month, respectively. In the validation phase, a strong correlation was found between the evaporative fraction derived from MPT and that observed by lysimeter, with R2 = 0.71, mean biased error = 0.04 mm day−1, root mean squared error = 0.62 mm day-1 and agreement index of 0.914. These results collectively support the effectiveness of the MPT model in accurately estimating ET across Udham Singh Nagar district. In essence, this research not only confirms the MPT model’s capability in ET estimation but also offers detailed insights into the spatial and temporal fluctuations of energy fluxes and daily ET rates.
Gate modulation of barrier height of unipolar vertically stacked monolayer ReS2/MoS2 heterojunction
Authors: Polumati Gowtham , Kolli Chandra Sekhar Reddy , Kumar Aayush , Salazar Mario Flores , De Luna Bugallo Andres , Sahatiya Parikshit
Published: September 2024

This study investigates vertically stacked CVD grown ReS2/MoS2 unipolar heterostructure device as Field Effect Transistor (FET) device wherein ReS2 on top acts as drain and MoS2 at bottom acts as source. The electrical measurements of ReS2/MoS2 FET device were carried out and variation in Ids (drain current) Vs Vds (drain voltage) for different Vgs (gate voltage) revealing the n-type device characteristics. Furthermore, the threshold voltage was calculated at the gate bias voltage corresponding to maximum transconductance (gm) value which is ~ 12 V. The mobility of the proposed ReS2/MoS2 heterojunction FET device was calculated as 60.97 cm2 V−1 s−1. The band structure of the fabricated vDW heterostructure was extracted utilizing ultraviolet photoelectron spectroscopy and the UV–visible spectroscopy revealing the formation of 2D electron gas (2DEG) at the ReS2/MoS2 interface which explains the high carrier mobility of the fabricated FET. The field effect behavior is studied by the modulation of the barrier height across heterojunction and detailed explanation is presented in terms of the charge transport across the heterojunction.
Detection of Alcoholic EEG signal using LASSO regression with metaheuristics algorithms based LSTM and enhanced artificial neural network classification algorithms
Authors: Manivannan Gowri Shankar , Mani Kalaiyarasi , Rajaguru Harikumar , Talawar Satish V.
Published: September 2024

The world has a higher count of death rates as a result of Alcohol consumption. Identification is possible because Alcoholic EEG waves have a certain behavior that is totally different compared to the non-alcoholic individual. The available approaches take longer to provide the feedback because they analyze the data manually. For this reason, in the present paper we propose a novel approach applied to detect alcoholic EEG signals automatically by using deep learning methods. Our strategy has advantages as far as fast detection is concerned; hence people can help immediately when there is a need. The potential for a significant decrease in deaths from alcohol poisoning and improvement to public health is presented by this advancement. In order to create clusters and classify the alcoholic EEG signals, this research uses a cascaded process. To begin with, an initial clustering and feature extraction is done by LASSO regression. After that, a variety of meta-heuristics algorithms like Particle Swarm Optimization (PSO), Binary Coding Harmony Search (BCHS) as well as Binary Dragonfly Algorithm (BDA) are employed for feature minimization. When this method is used, normal and alcoholic EEG signals may be differentiated using non-linear features. PSO, BCHS, and BDA features allow for estimation of statistical parameters through t-test, Friedman statistic test, Mann-Whitney U test, and Z-Score with corresponding p-values for alcoholic EEG signals. Lastly, classification is done by the use of support vector machines (SVM) (including linear, polynomial, and Gaussian kernels), random forests, artificial neural networks (ANN), enhanced artificial neural networks (EANN), and LSTM models. Results showed that LASSO regression with BDA-based EANN proposed classifier have a classification accuracy of 99.59%, indicating that our method is highly accurate at classifying alcoholic EEG signals.
Long-term changes in wearable sensor data in people with and without Long Covid
Authors: Radin Jennifer M. , Vogel Julia Moore , Delgado Felipe , Coughlin Erin , Gadaleta Matteo , Pandit Jay A. , Steinhubl Steven R.
Published: September 2024

To better understand the impact of Long COVID on an individual, we explored changes in daily wearable data (step count, resting heart rate (RHR), and sleep quantity) for up to one year in individuals relative to their pre-infection baseline among 279 people with and 274 without long COVID. Participants with Long COVID, defined as symptoms lasting for 30 days or longer, following a SARS-CoV-2 infection had significantly different RHR and activity trajectories than those who did not report Long COVID and were also more likely to be women, younger, unvaccinated, and report more acute-phase (first 2 weeks) symptoms than those without Long COVID. Demographic, vaccine, and acute-phase sensor data differences could be used for early identification of individuals most likely to develop Long COVID complications and track objective evidence of the therapeutic efficacy of any interventions.

Trial Registration: https://classic.clinicaltrials.gov/ct2/show/NCT04336020.
Single-step in situ synthesis of bimetallic catalysts via a gas-phase route: the case of PdZn–ZnO
Authors: Kokanović Andrija , Pupavac Dunja , Chenot Stéphane , Guilet Stéphane , Opsenica Igor M. , Stankic Slavica
Published: September 2024

In this study, we explore the catalytic activity of highly pure PdZn–ZnO nanopowder, synthesized via an innovative metal–organic chemical vapor synthesis (MOCVS) method.
Construction of a flow-through catalytic reactor employing O3–Fe/TiO2 for efficient catalytic ozonation disinfection
Authors: Li Jiaxuan , Chen Xin , Li Siyu , Mei Kunrong , Liu Lequan , Ye Jinhua
Published: September 2024

An O3–Fe/TiO2 reactor is designed for efficient air disinfection by catalytically converting ozone into reactive oxygen species (ROS).
Exploring the variability of PFAS in urban sewage: a comparison of emissions in commercial versus municipal urban areas
Authors: N. Krlovic , E. Saracevic , J. Derx , C. Gundacker , J. Krampe , N. Kreuzinger , M. Zessner , O. Zoboli
Published: September 2024

PFAS in an urban environment can come from various sources. The main activity in the area, i.e. commercial versus municipal, can influence the overall loads and speciation of PFAS in the examined wastewater.
A comprehensive study on the physicochemical characteristics of faecal sludge from septic tank and single pit latrine facilities in a typical semi-urban Indian town: a case study of Rajasthan, India
Authors: Jothinathan Harishvar , Singh Ajit Pratap
Published: September 2024

Faecal sludge (FS) samples were analysed to assess their characteristics. FS has high chemical oxygen demand, ranging from 4406 to 160 000 mg l−1, influenced by sludge age, sanitation type, and inflow/outflow to onsite sanitation contaminants.
Zein and gum arabic nanoparticles: potential enhancers of immunomodulatory functional activity of selenium-containing peptides
Authors: Tang Wenqian , Luo Xieqi , Fan Fengjiao , Sun Xinyang , Jiang Xiaoyi , Li Peng , Ding Jian , Lin Qinlu , Zhao Siming , Cheng Yunhui , Fang Yong
Published: September 2024

ZTGNs reversed the organ indices and GSH levels, normalized cytokines levels and mRNA expression, and enriched intestinal flora diversity in mice. This proves that ZTGNs might enhance the immunomodulatory properties of selenium-containing peptides.
Multi-omics analysis reveals that agaro-oligosaccharides with different degrees of polymerization alleviate colitis in mice by regulating intestinal flora and arginine synthesis
Authors: Yuan Long , Liu Chunhui , Li Bolun , Wang Sai , Sun Jianan , Mao Xiangzhao
Published: September 2024

Inflammatory bowel disease (IBD) is a common chronic disease with a complex etiology, characterized by body weight loss, intestinal barrier damage, and an imbalance of intestinal flora, posing a significant threat to people's health.
Microstructural stiffness engineering of low dimensional metal halide perovskites for efficient X-ray imaging
Authors: Tang Yangmin , Pu Guiqiang , Kang Chengbin , Li Chenyang , Wang Xiaoze , Wang Machao , Bi Hui , Chen Wei , Wang Jiacheng
Published: September 2024

We report microstructural stiffness engineering of metal halide perovskites, resulting in an increase in the Young's modulus from 15.6 to 18.3 GPa. This leads to a 10-fold and 16-fold enhancement in the luminescence intensity and quantum yield.
A biocompatible polydopamine platform for targeted delivery of nicotinamide mononucleotide and boosting NAD+ levels in the brain
Authors: Cai Xiaoli , Huang Yuteng , Wang Ting , Wang Ziping , Jiao Lei , Liao Jingling , Zhou Li , Zhu Chengzhou , Rong Shuang
Published: September 2024

A biocompatible polydopamine platform to target-deliver NMN for boosting brain NAD+ levels is developed for the first time.
Ru nanoparticle-loaded amorphous CoMoP as an efficient electrocatalyst for alkaline water/seawater hydrogen evolution
Authors: Li Wen-Jing , Tian Xin-Jie , Sun Hai-Yi , Yang Xue-Ying , Ouyang Denghao , Li Guodong , Liu Bin , Chai Yong-Ming , Dong Bin
Published: September 2024

A low-cost carrier is developed and the size of Ru nanoparticles is reduced to enhance the performance of Ru catalysts used in the hydrogen evolution reaction (HER).
Halogenated carborane molecular ferroelectric crystals with high-temperature phase transition
Authors: Guo Wenjing , Cheng Wenkang , Li Yuting , Wei Zhenhong , Cai Hu
Published: September 2024

Five cage-like halogenated o-carborane molecular ferroelectric crystals were successfully obtained with the highest Tc reaching 437 K. This provides a novel avenue for the further design of high Tc carborane ferroelectric crystals.
Surface-enhanced Raman spectroscopy (SERS) for the diagnosis of acute myocardial infarction (AMI) using blood serum samples
Authors: Naz Maira , Shafique Hira , Majeed Muhammad Irfan , Nawaz Haq , Rashid Nosheen , Alshammari Abdulrahman , Albekairi Norah A. , Amber Arooj , Zohaib Muhammad , Shahid Urwa , Zafar Fareeha , Ali Muhammad , Shahid Habiba
Published: September 2024

Surface-enhanced Raman spectroscopy is employed for the characterization and diagnosis of acute myocardial infarction using blood serum samples.
Synthesis and characterization of micro-/nano-α-Fe2O3 for photocatalytic dye degradation
Authors: Uttam Pandit Vikram Rama , Parshuram Jadhav Ganesh Kavita , Sakharam Jawale Vivekanand Mangal , Dubepatil Rohit , Gurao Rajendra , Late Dattatray J.
Published: September 2024

Photocatalytic activity using micro-/nano-α-Fe2O3 on a large scale was carried out using a sol–gel autocombustion method.
Synthesis of colicin Ia neoglycoproteins: tools towards glyco-engineering of bacterial cell surfaces
Authors: Hatton Natasha E. , Wilson Laurence G. , Baumann Christoph G. , Fascione Martin A.
Published: September 2024

Herein we demonstrate organocatalyst-mediated protein aldol ligation (OPAL) modification of the bacteriocidin colicin Ia to afford mannose-presenting neoglycoproteins with potential utility for non-genetic glyco-engineering of E. coli cell surfaces.
Vitamin B12-catalyzed coupling reaction of nitroalkanes and diazo compounds
Authors: Zhang Zheng , Chen Meiyu , Zheng Guojun
Published: September 2024

Vitamin B12 is a natural and environmentally friendly catalyst.
Enantioselective total synthesis of (+)-cylindricine B
Authors: Dukes Dallas M. , Atanassov Victor K. , Smith Joel M.
Published: September 2024

A concise enantioselective synthesis of the marine alkaloid (+)-cylindricine B proceeds in 5 or 6 steps and hinges on dearomative retrosynthetic logic.
Synthesis, optical, electronic and magnetic studies of air-stable chiral Cu(ii) chlorides
Authors: Azmy Ali , Mudiyanselage Nivarthana W. Y. A. Y. , Nassar Kamal E. S. , Pham Mike , Zibouche Nourdine , Phan Manh-Huong , Spanopoulos Ioannis
Published: September 2024

The development of polar MHSs with competitive chiroptical and magnetic properties, featuring record air stability of over a year.
Restricting the over-oxidation of active sites in high-entropy electrocatalysts towards ultra-stabilized oxygen evolution in alkaline water electrolysis
Authors: Zhang Yimin , Kang Jianli , Xie Haonan , Yin Hongxia , Zhang Zhijia , Ma Yuhan , Sun Guangxin , Liu Enzuo , Ma Liying , Chen Biao , Sha Junwei , Qian Lihua , Hu Wenbin , He Chunnian , Zhao Naiqin
Published: September 2024

Based on ionic electronegativity, theoretical calculation guided the synthesis of np-MnFeCoNiCuOOH exhibiting ultra-stabilized oxygen evolution in alkaline water electrolysis.
Encapsulation of telmisartan inside insulinoma-cell-derived extracellular vesicles outperformed biomimetic nanovesicles in modulating the pancreatic inflammatory microenvironment
Authors: Singh Anjali , Pore Subrata Kumar , Bhattacharyya Jayanta
Published: September 2024

Diabetes mellitus (DM) is a chronic metabolic condition, characterized by hyperglycaemia, oxidative imbalance, pancreatic β-cell death, and insulin insufficiency.