bluuebunny/crossref_metadata_2025 huggingface dataset:
A randomized, double‐blind, placebo‐controlled study of Cistanche tubulosa and Ginkgo biloba extracts for the improvement of cognitive function in middle‐aged and elderly people
Authors: Chen Liang , Liu Xin , Zheng Jianheng , Li Gang , Yang Binrui , He Anli , Liu Hongyue , Liang Yingzhen , Wang Wen’ an , Du Jun
Published: July 2024

Mild cognitive impairment poses an increasing challenge to middle‐aged and elderly populations. Traditional Chinese medicinal herbs like Cistanche tubulosa and Ginkgo biloba (CG) have been proposed as potential agents to improve cognitive and memory functions. A randomized controlled trial involving 100 Chinese middle‐aged and elderly participants was conducted to investigate the potential synergistic effects of CG on cognitive function in individuals at risk of neurodegenerative diseases. Over 90 days, both CG group and placebo group received two tablets daily, with each pair of CG tablets containing 72 mg echinacoside and 27 mg flavonol glycosides. Cognitive functions were assessed using multiple scales and blood biomarkers were determined at baseline, Day 45, and Day 90. The CG group exhibited significant improvements in the scores of Mini‐Mental State Examination (26.5 at baseline vs. 27.1 at Day 90, p < 0.001), Montreal Cognitive Assessment (23.4 at baseline vs. 25.3 at Day 90, p < 0.001), and World Health Organization Quality of Life (81.6 at baseline vs. 84.2 at Day 90, p < 0.001), all surpassing scores in placebo group. Notably, both the Cognitrax matrix test and the Wechsler Memory Scale‐Revised demonstrated enhanced memory functions, including long‐term and delayed memory, after CG intervention. Moreover, cognitive‐related blood biomarkers, including total tau, pT181, pS199, pT231, pS396, and thyroid‐stimulating hormone, significantly decreased, whereas triiodothyronine and free triiodothyronine significantly increased. No treatment‐related adverse events were reported, and routine blood and urine tests remained stable. These findings indicated that CG supplementation could potentially serve as an effective supplementary solution for enhancing cognitive and memory functions.
Association of risk assessment at diagnosis with healthcare resource utilization and health‐related quality of life outcomes in pulmonary arterial hypertension
Authors: Lawrie Allan , Hamilton Neil , Wood Steven , Exposto Fernando , Muzwidzwa Ruvimbo , Raiteri Louise , Beaudet Amélie , Muller Audrey , Sauter Rafael , Pillai Nadia , Kiely David G. ,   ASPIRE Consortium
Published: July 2024

We aimed to describe the clinical characteristics, healthcare resource utilization (HCRU) and costs, health‐related quality of life (HRQoL), and survival for patients with pulmonary arterial hypertension (PAH), stratified by 1‐year mortality risk at diagnosis. Adults diagnosed with PAH at the Sheffield Pulmonary Vascular Disease Unit between 2012 and 2019 were included. Patients were categorized as low, intermediate, or high risk for 1‐year mortality at diagnosis. Demographics, clinical characteristics, comorbidities, HCRU, costs, HRQoL, and survival were analyzed. Overall, 1717 patients were included: 72 (5%) at low risk, 941 (62%) at intermediate risk, and 496 (33%) at high risk. Low‐risk patients had lower HCRU prediagnosis and 1‐year postdiagnosis than intermediate‐ or high‐risk patients. Postdiagnosis, there were significant changes in HCRU, particularly inpatient hospitalizations and accident and emergency (A&E) visits among high‐risk patients. At 3 years postdiagnosis, HCRU for all measures was similar across risk groups. Low‐risk patients had lower EmPHasis‐10 scores (indicating better HRQoL) at diagnosis and at 1‐year follow‐up compared with intermediate‐ and high‐risk patients; only the score in the high‐risk group improved. Median overall survival decreased as risk category increased in analyzed subgroups. Low‐risk status was associated with better 1‐year survival and HRQoL compared with intermediate‐ and high‐risk patients. HCRU decreased in high‐risk patients postdiagnosis, with the most marked reduction in A&E admissions. The pattern of decreased per‐patient inpatient hospitalizations and A&E visits at 3 years postdiagnosis suggests that a diagnosis of PAH helps to decrease HCRU in areas that are key drivers of costs.
A modular model for reliability analysis model of PMS with multiple K/N subsystems and mixed shocks
Authors: Wang Weijie , Li Xiangyu , Xiong Xiaoyan
Published: July 2024

In this article, a modular model is proposed for the reliability modeling of phased mission systems (PMSs) with complicated system behaviors. By the modular method, the system is divided into several levels: system, subsystem, and components. At the component level, the shock effect, including self‐degradation, additional wear and damage caused by shocks, is considered and the component reliability is evaluated. Then, the reliability modeling method of the K/N system consisting of multiple K/N subsystems is proposed, by a mathematics reasoning method. The correctness of the proposed method is also verified by a Monte Carlo (MC) simulation procedure. At last, the modular method is applied at the system level, and the reliability of a practical engineering case, the attitude and orbit control system (AOCS), is evaluated for illustration. Meanwhile, the parameter sensitivity analysis is also carried out for implementation.
A sequential, multiple assignment, randomized trial design with a tailoring function
Authors: Hartman Holly , Schipper Matthew , Kidwell Kelley
Published: July 2024

We present a trial design for sequential multiple assignment randomized trials (SMARTs) that use a tailoring function instead of a binary tailoring variable allowing for simultaneous development of the tailoring variable and estimation of dynamic treatment regimens (DTRs). We apply methods for developing DTRs from observational data: tree‐based regression learning and Q‐learning. We compare this to a balanced randomized SMART with equal re‐randomization probabilities and a typical SMART design where re‐randomization depends on a binary tailoring variable and DTRs are analyzed with weighted and replicated regression. This project addresses a gap in clinical trial methodology by presenting SMARTs where second stage treatment is based on a continuous outcome removing the need for a binary tailoring variable. We demonstrate that data from a SMART using a tailoring function can be used to efficiently estimate DTRs and is more flexible under varying scenarios than a SMART using a tailoring variable.
Phosphorus‐Based Polymeric Flame Retardants – Recent Advances and Perspectives
Authors: Singh Indresh , Sivaramakrishna Akella
Published: July 2024

Among the various fire‐retardants (FRs) known, phosphorus is vital to the development of effective FRs due to its flexibility. Additionally, the additives and combinations of phosphorus with various multicomponent moieties (e. g. P−Si, P−P, P−B, etc.) can serve the purpose in different phases to improve flame retardance properties. With an increased cognizance of recyclable, eco‐friendly, and bio‐based materials, phosphine oxide‐based materials/coatings can fulfill the criteria for flawless and future FRs. In this regard, the present review highlights the most promising organophosphorus‐based compositions as non‐intrusive FRs. The classification, synthetic methods, related mechanisms, and high‐end FR applications of various recently developed organophosphorus‐based molecules and materials are demonstrated. Among various organophosphorus compounds, the phosphorus‐based polyurethane materials display remarkable FR properties and non‐toxic behavior. Notably, the flame retardance of the epoxy resins is enhanced significantly with the presence of more P=O bonds and amino groups. The limitations and advantages of organophosphorus‐based materials are compared with the traditional FRs. Also, the challenges persisting in improving current flame‐retardant materials need to be addressed. However, the success of these materials and treatment methods strongly depends on the ability to impart desired functionality, durability, and scalability without compromising environmental problems.
Optimal Oxophilicity at the Fe‐Nx Interface Enhances the Generation of Singlet Oxygen for Efficient Fenton‐Like Catalysis
Authors: Fan Yafei , Chu Menghui , Li Haibin , Sun Zhaoli , Kong Dezhi , Yao Jianfei , Wang Guo , Wang Yifeng , Zhu Huai‐Yong
Published: July 2024

In the pursuit of efficient singlet oxygen generation in Fenton‐like catalysis, the utilization of single‐atom catalysts (SACs) emerges as a highly desired strategy. Here, a discovery is reported that the single‐atom Fe coordinated with five N‐atoms on N‐doped porous carbon, denoted as Fe‐N5/NC, outperform its counterparts, those coordinated with four (Fe‐N4/NC) or six N‐atoms (Fe‐N6/NC), as well as state‐of‐the‐art SACs comprising other transition metals. Thus, Fe‐N5/NC exhibits exceptional efficacy in activating peroxymonosulfate for the degradation of organic pollutants. The coordination number of N‐atoms can be readily adjusted by pyrolysis of pre‐assembly structures consisting of Fe3+ and various isomers of phenylenediamine. Fe‐N5/NC displayed outstanding tolerance to environmental disturbances and minimal iron leaching when incorporated into a membrane reactor. A mechanistic study reveals that the axial ligand N reduces the contribution of Fe‐3d orbitals in LUMO and increases the LUMO energy of Fe‐N5/NC. This, in turn, reduces the oxophilicity of the Fe center, promoting the reactivity of *OO intermediate—a pivotal step for yielding singlet oxygen and the rate‐determining step. These findings unveil the significance of manipulating the oxophilicity of metal atoms in single‐atom catalysis and highlight the potential to augment Fenton‐like catalysis performance using Fe‐SACs.
Semantic similarity loss for neural source code summarization
Authors: Su Chia‐Yi , McMillan Collin
Published: July 2024

This paper presents a procedure for and evaluation of using a semantic similarity metric as a loss function for neural source code summarization. Code summarization is the task of writing natural language descriptions of source code. Neural code summarization refers to automated techniques for generating these descriptions using neural networks. Almost all current approaches involve neural networks as either standalone models or as part of a pretrained large language models, for example, GPT, Codex, and LLaMA. Yet almost all also use a categorical cross‐entropy (CCE) loss function for network optimization. Two problems with CCE are that (1) it computes loss over each word prediction one‐at‐a‐time, rather than evaluating a whole sentence, and (2) it requires a perfect prediction, leaving no room for partial credit for synonyms. In this paper, we extend our previous work on semantic similarity metrics to show a procedure for using semantic similarity as a loss function to alleviate this problem, and we evaluate this procedure in several settings in both metrics‐driven and human studies. In essence, we propose to use a semantic similarity metric to calculate loss over the whole output sentence prediction per training batch, rather than just loss for each word. We also propose to combine our loss with CCE for each word, which streamlines the training process compared to baselines. We evaluate our approach over several baselines and report improvement in the vast majority of conditions.
Wearable and Multiplexed Biosensors based on Oxide Field‐Effect Transistors
Authors: Ren Huihui , Zhang Siyu , Li Dingwei , Tang Yingjie , Chen Yitong , Wang Yan , Liu Guolei , Li Fanfan , Liu Lihua , Huang Qi , Xing Lixiang , Chen Xiaopeng , Wang Juan , Zhu Bowen
Published: July 2024

Wearable sensors designed for continuous, non‐invasive monitoring of physicochemical signals are important for portable healthcare. Oxide field‐effect transistor (FET)‐type biosensors provide high sensitivity and scalability. However, they face challenges in mechanical flexibility, multiplexed sensing of different modules, and the absence of integrated on‐site signal processing and wireless transmission functionalities for wearable sensing. In this work, a fully integrated wearable oxide FET‐based biosensor array is developed to facilitate the multiplexed and simultaneous measurement of ion concentrations (H+, Na+, K+) and temperature. The FET‐sensor array is achieved by utilizing a solution‐processed ultrathin (≈6 nm thick) In2O3 active channel layer, exhibiting high compatibility with standard semiconductor technology, good mechanical flexibility, high uniformity, and low operational voltage of 0.005 V. This work provides an effective method to enable oxide FET‐based biosensors for the fusion of multiplexed physicochemical information and wearable health monitoring applications.
Overfeeding copper during rearing affects the liver function and fertility of replacement dairy heifers
Authors: McCaughern James H. , Mackenzie Alexander M. , Bleach Emma C. L. , Sinclair Liam A.
Published: July 2024

Background

Oversupply of dietary copper (Cu) is common among UK dairy herds, but studies on the long‐term outcomes of this oversupply are scarce.

Methods

A longitudinal study was undertaken to determine the long‐term implications when 80 Holstein‒Friesian heifers with a mean (±standard error) age of 4.1 ± 0.1 months and a mean liveweight of 137 ± 2.4 kg were fed a recommended (R; 16 mg/kg dry matter [DM]) or high (H; 32 mg/kg DM) dietary Cu concentration until 6 weeks prior to calving.

Results

Hepatic Cu concentrations in both treatment groups were elevated into the ranges used to diagnose chronic Cu toxicity in cattle at 6.9 months of age (798 ± 46.4 mg/kg DM for H vs. 643 ± 35.4 mg/kg DM for R), with associated evidence of liver damage. Hepatic Cu concentrations then returned to normality but remained higher (p < 0.001) for heifers fed H than for those fed R and were associated with a reduced (p = 0.044) conception rate to first and second services (73.7 ± 8.05% for H vs. 91.2 ± 7.68% for R).

Limitation

This retrospective analysis identified pre‐study liver damage, which may have affected results.

Conclusions

Supplying Cu in excess of requirements resulted in liver damage and reduced conception rates.
Well-posedness for a class of pseudo-differential hyperbolic equations on the torus
Authors: Cardona Duván , Delgado Julio , Ruzhansky Michael
Published: July 2024

In this paper we establish the well-posedness of the Cauchy problem for a class of pseudo-differential hyperbolic equations on the torus. The class considered here includes a space-like fractional order Laplacians. By applying the toroidal pseudo-differential calculus we establish regularity estimates, existence and uniqueness in the scale of the standard Sobolev spaces on the torus.
Aqp4a and Trpv4 mediate regulatory cell volume increase for swimming maintenance of marine fish spermatozoa
Authors: Castro-Arnau Júlia , Chauvigné François , Toft-Bertelsen Trine L. , Finn Roderick Nigel , MacAulay Nanna , Cerdà Joan
Published: July 2024

Volume regulation is essential for cell homeostasis and physiological function. Amongst the sensory molecules that have been associated with volume regulation is the transient receptor potential vanilloid 4 (TRPV4), which is a non-selective cation channel that in conjunction with aquaporins, typically controls regulatory volume decrease (RVD). Here we show that the interaction between orthologous AQP4 (Aqp4a) and TRPV4 (Trpv4) is important for regulatory volume increase (RVI) in post-activated marine fish spermatozoa under high osmotic stress. Based upon electrophysiological, volumetric, and in vivo and ex vivo functional experiments using the pharmacological and immunological inhibition of Aqp4a and Trpv4 our model suggests that upon ejaculation and exposure to the hypertonic seawater, spermatozoon shrinkage is initially mediated by water efflux through Aqp1aa in the flagellar tail. The shrinkage results in an increase in intracellular Ca2+ concentration, and the activation of sperm motility and a Na+/K+/2Cl− (NKCC1) cotransporter. The activity of NKCC1 is required for the initiation of cell swelling, which secondarily activates the Aqp4a-Trpv4 complex to facilitate the influx of water via Aqp4a-M43 and Ca2+ via Trpv4 and L-type channels for the mediation of RVI. The inhibitory experiments show that blocking of each of these events prevents either shrinkage or RVI. Our data thus reveal that post-activated marine fish spermatozoa are capable of initiating RVI under a high hypertonic stress, which is essential for the maintenance of sperm motility.
Soft pads for robotic limbs: achieving human finger compliance via finite element optimization
Authors: Kargar Seyyed Masoud , Berselli Giovanni
Published: July 2024

Human fingers possess compliant contact interfaces with predetermined compliance properties. Replicating these compliance properties in robotic limbs, particularly anthropomorphic hands, can significantly impact grasp stability and contact area. To address the limitations of homogeneous layers of soft material commonly used in anthropomorphic hands, this paper proposes optimizing differentiated structures to design soft pads, which consist of a continuous external layer (skin) coupled with an internal layer featuring voids. To achieve the desired compliance properties replicating those of human fingers, the paper introduces five distinct patterns for differentiated structures, along with their corresponding finite element analysis (FEA) models. Subsequently, by formulating an appropriate optimization function, the shapes of these patterns have been optimized to match the compliance of the human finger, and it has been demonstrated that one of the proposed and optimized pads closely approximates this target through the proposed methodology. The results affirm that this approach offers an effective solution for designing soft pads whose behavior needs to be aligned with the compliance of a specific target.
Severance savings accounts and life-cycle savings
Authors: Azevedo Rafael , Bettoni Luis , Santos Marcelo
Published: July 2024

Severance savings accounts (SSA) is an important government program aimed at protecting laid-off workers and stimulating savings. We analyze the distributive and aggregate effects of SSA in a rich life-cycle model with heterogeneous agents and incomplete markets. The model is estimated to be consistent with micro and macro data from Brazil. Our analysis reveals that, despite a decrease in voluntary savings, the policy expands aggregate savings, output, and wages, leading to long-run welfare gains. We show that although better risk sharing is important for our findings, the bulk of the gains come from improved efficiency as labor productivity increases and labor supply is reallocated towards highly educated workers and the early stages of the life cycle where agents are generally poorer and leisure is less valued. Interestingly, most of the gains we find accrue to less educated agents as the distribution of this group is skewed towards the informal sector, and they do not directly incur the additional burden from the increase in contributions. We also explore an alternative policy design in which households are allowed to access their severance savings accounts only after retirement, as in a defined contribution pension system. We find that despite greater uncertainty in medical costs later in life, households prefer a more flexible system that provides access to the SSA fund during working-age and after retirement.
A pH-dependent shift of redox cofactor specificity in a benzyl alcohol dehydrogenase of aromatoleum aromaticum EbN1
Authors: Gemmecker Yvonne , Winiarska Agnieszka , Hege Dominik , Kahnt Jörg , Seubert Andreas , Szaleniec Maciej , Heider Johann
Published: July 2024

We characterise a reversible bacterial zinc-containing benzyl alcohol dehydrogenase (BaDH) accepting either NAD+ or NADP+ as a redox cofactor. Remarkably, its redox cofactor specificity is pH-dependent with the phosphorylated cofactors favored at lower and the dephospho-forms at higher pH. BaDH also shows different steady-state kinetic behavior with the two cofactor forms. From a structural model, the pH-dependent shift may affect the charge of a histidine in the 2′-phosphate-binding pocket of the redox cofactor binding site. The enzyme is phylogenetically affiliated to a new subbranch of the Zn-containing alcohol dehydrogenases, which share this conserved residue. BaDH appears to have some specificity for its substrate, but also turns over many substituted benzyl alcohol and benzaldehyde variants, as well as compounds containing a conjugated C=C double bond with the aldehyde carbonyl group. However, compounds with an sp3-hybridised C next to the alcohol/aldehyde group are not or only weakly turned over. The enzyme appears to contain a Zn in its catalytic site and a mixture of Zn and Fe in its structural metal-binding site. Moreover, we demonstrate the use of BaDH in an enzyme cascade reaction with an acid-reducing tungsten enzyme to reduce benzoate to benzyl alcohol.

Key points

•Zn-containing BaDH has activity with either NAD+or NADP+at different pH optima.

•BaDH converts a broad range of substrates.

•BaDH is used in a cascade reaction for the reduction of benzoate to benzyl alcohol.
Structural diversification of vitamin D using microbial biotransformations
Authors: García-Domínguez Mario , Gutiérrez-del-Río Ignacio , Villar Claudio J. , Perez-Gomez Anabel , Sancho-Martinez Ignacio , Lombó Felipe
Published: July 2024

Vitamin D deficiencies are linked to multiple human diseases. Optimizing its synthesis, physicochemical properties, and delivery systems while minimizing side effects is of clinical relevance and is of great medical and industrial interest. Biotechnological techniques may render new modified forms of vitamin D that may exhibit improved absorption, stability, or targeted physiological effects. Novel modified vitamin D derivatives hold promise for developing future therapeutic approaches and addressing specific health concerns related to vitamin D deficiency or impaired metabolism, such as avoiding hypercalcemic effects. Identifying and engineering key enzymes and biosynthetic pathways involved, as well as developing efficient cultures, are therefore of outmost importance and subject of intense research. Moreover, we elaborate on the critical role that microbial bioconversions might play in the a la carte design, synthesis, and production of novel, more efficient, and safer forms of vitamin D and its analogs. In summary, the novelty of this work resides in the detailed description of the physiological, medical, biochemical, and epidemiological aspects of vitamin D supplementation and the steps towards the enhanced and simplified industrial production of this family of bioactives relying on microbial enzymes.

Key points

• Liver or kidney pathologies may hamper vitamin D biosynthesis

• Actinomycetes are able to carry out 1α- or 25-hydroxylation on vitamin D precursors
Revealing endogenous conditions for Peto’s paradox via an ordinary differential equation model
Authors: Kan Haichun , Chen Yu
Published: July 2024

Cancer, a disease intimately linked to cellular mutations, is commonly believed to exhibit a positive association with the cell count and lifespan of a species. Despite this assumption, the observed uniformity in cancer rates across species, referred to as the Peto’s paradox, presents a conundrum. Recognizing that tumour progression is not solely dependent on cancer cells but involves intricate interactions among various cell types, this study employed a Lotka-Volterra (LV) ordinary differential equation model to analyze the evolution of cancerous cells and the cancer incidence in an immune environment. As a result, this study uncovered the sufficient conditions underlying the absence of correlation in Peto’s paradox and provide insights into the reasons for the equitable distribution of cancer incidence across diverse species by applying nondimensionalization and drawing an analogy between the characteristic time interval for the variation of cell populations in the ODE model and that of cell cycles of a species.
Aflibercept im klinischen Alltag: die AURIGA-Studie
Authors: Wachtlin Joachim , Kaymak Hakan , Hoerauf Hans , Allmeier Helmut , Machewitz Tobias , Scholz Paula , Schürks Markus , Feltgen Nicolas
Published: July 2024

Hintergrund

AURIGA ist die größte prospektive Real-World-Studie zur Behandlung eines Makulaödems (MÖ) nach retinalem Venenverschluss (RVV) oder eines diabetischen Makulaödems mit intravitrealem Aflibercept 2 mg (IVT-AFL). Hier werden die 24-Monats-Daten der deutschen behandlungsnaiven RVV-Kohorte mit MÖ präsentiert.

Methoden

Behandlungsnaive RVV-Patienten mit MÖ wurden mit IVT-AFL 2 mg in der klinischen Routine therapiert. Primärer Endpunkt war die mittlere Änderung des Visus (ETDRS-Buchstaben) zu Monat 12 gegenüber dem Ausgangswert. Die Analyse erfolgte deskriptiv.

Ergebnisse

Es wurden 130 Patienten mit RVV (n = 61 [46,9 %] mit Zentralvenenverschluss, n = 69 [53,1 %] mit Venenastverschluss) untersucht. Im Mittel (± SD) verblieben die RVV-Patienten für 18,4 ± 7,4 Monate in der Studie. Der mittlere Visusgewinn [95 % Konfidenzintervall] betrug in der Gesamtkohorte +10,9 [7,5; 14,2] Buchstaben zu Monat 12 und +9,7 [6,1; 13,3] zu Monat 24 (Baseline 56,5 ± 18,9 Buchstaben). Nach 24 Monaten hatten 67 % der RVV-Patienten ≥5 Buchstaben, 40 % ≥ 15 Buchstaben gewonnen. Von Baseline betrug die mittlere Injektionszahl 4,4 ± 1,3 bis Monat 6, 6,2 ± 2,7 bis Monat 12 und 8,2 ± 4,5 bis Monat 24. Die durchschnittliche Reduktion der zentralen Netzhautdicke (Ausgangswert 507 ± 177 µm) betrug in der Gesamtkohorte −206 (−252; −160) µm nach 12 Monaten und −219 (−263; −175) µm nach 24 Monaten. Das Sicherheitsprofil entsprach dem früherer Studien.

Diskussion

In der deutschen AURIGA-Kohorte behandlungsnaiver Patienten mit MÖ infolge RVV unter IVT-AFL-2 mg-Behandlung zeigten sich im klinischen Alltag ein rascher und klinisch relevanter Visusgewinn sowie eine Reduktion der zentralen Netzhautdicke. Diese wurden trotz niedriger Injektionsfrequenz ab Monat 6 über 24 Monate weitestgehend erhalten.
Clustering with Minimum Spanning Trees: How Good Can It Be?
Authors: Gagolewski Marek , Cena Anna , Bartoszuk Maciej , Brzozowski Łukasz
Published: July 2024

Minimum spanning trees (MSTs) provide a convenient representation of datasets in numerous pattern recognition activities. Moreover, they are relatively fast to compute. In this paper, we quantify the extent to which they are meaningful in low-dimensional partitional data clustering tasks. By identifying the upper bounds for the agreement between the best (oracle) algorithm and the expert labels from a large battery of benchmark data, we discover that MST methods can be very competitive. Next, we review, study, extend, and generalise a few existing, state-of-the-art MST-based partitioning schemes. This leads to some new noteworthy approaches. Overall, the Genie and the information-theoretic methods often outperform the non-MST algorithms such as K-means, Gaussian mixtures, spectral clustering, Birch, density-based, and classical hierarchical agglomerative procedures. Nevertheless, we identify that there is still some room for improvement, and thus the development of novel algorithms is encouraged.
Spinal posture, mobility, and position sense in adolescents with chest wall deformities: a comparison of pectus excavatum, pectus carinatum and healthy peers
Authors: METE Oguzhan , IŞIK Hakan , PİRİNÇÇİ Cansu ŞAHBAZ , YAŞA Mustafa Ertuğrul , SAPMAZ Ersin
Published: July 2024

Purpose

The study aimed to compare spinal posture, mobility, and position sense in adolescents with pectus excavatum (PE), pectus carinatum (PC), and healthy control (HC).

Methods

22 with PE, 22 with PC, and 21 HC were included in the study. The spinal posture (thoracic kyphosis, lumbar lordosis, pelvic tilt, thoracic, lumbar, pelvic lateral tilt angles) and mobility (thoracic, lumbar, hip/sacral, and overall, in the sagittal and frontal plane) with the spinal mouse, and spinal position sense (repositing errors) with the inclinometer were assessed.

Results

The thoracic kyphosis angle of PE and PC was higher than in HC (p < 0.001; p = 0.001). Hip/sacral mobility in the sagittal plane was lower in the PE and PC than control, respectively (p < 0.001; p < 0.001). Overall sagittal spinal mobility (p:0.007) and hip/sacral mobility in the frontal plane (p:0.002) were lower in the PC than in HC. Overall frontal spinal mobility was lower in the PE and PC than in HC (p:0.002; p:0.014). The PE and PC repositing errors were higher (p < 0.001; p:0.014).

Conclusion

The study found that adolescents with PE and PC had decreased spinal mobility, spinal alignment disorders, and a decline in spinal position sense. It is important not to overlook the spine during physical examinations of adolescents with chest wall deformities. In clinical practice, we suggest that adolescents with chest deformities should undergo a spine evaluation and be referred for physical therapy to manage spinal disorders.
Screening of voice and vocal tract changes in professional wind instrument players
Authors: El-Demerdash Ahmed M. , Hafez Nirvana G. , Tanyous Hanaa N. , Rezk Kerollos M. , Shadi Mariam S.
Published: July 2024

Purpose

Playing wind instruments is a strenuous task on the larynx, predisposing players to voice disorders. This study aims to evaluate potential vocal symptoms and vocal tract alterations in professional wind instrumentalists.

Methods

In this cross-sectional study, 26 male military subjects were interviewed, completed the voice handicap index (VHI) -10 questionnaire, and subjected to auditory-perceptual assessment, neck examination, rigid laryngostroboscopy and flexible nasofiberoscopy both before and during instrument playing.

Results

All participants had vocal fatigue symptoms, around one-quarter complained of voice change, one-quarter complained of shortness of breath while or after performing, and one-third complained of neck symptoms. The average score of VHI-10 was 16.2 ± 6.5, and approximately three-quarters of participants scored above the cut-off point. There were no significant correlations between age, years of instrument playing, average hours of daily practice, and VHI-10. Participants with neck symptoms had significantly higher VHI-10 scores. Those (around one-fifth) with an external neck swelling during Valsalva maneuver had a significantly higher VHI-10 score. Dysphonia, mainly mild and of strained, leaky quality, was detected in almost one-third of participants. While the instrument was being played, the vocal folds were somewhat adducted, and the vocal tract became more compressed as the task became more demanding. The most frequent observations in the vocal tract examination were hyperemia of the vocal folds or all over the laryngeal and pharyngeal mucosa, excessive secretions over the vocal folds, signs of hyperadduction, arytenoid edema, and phonatory waste.

Conclusion

Wind instrumentalists frequently experience voice disorders, which necessitate further care and investigation.
The German cochlear implant registry: one year experience and first results on demographic data
Authors: Stöver T. , Plontke S. K. , Lai W. K. , Zahnert T. , Guntinas-Lichius O. , Welkoborsky H-J. , Aschendorff A. , Deitmer T. , Loth A. , Lang S. , Dazert S.
Published: July 2024

Purpose

Clinical registries have great potential for quality control of medical procedures regarding the indications, therapeutic processes and results, including their possible complications. This is particularly true when providing patients with severe hearing loss or deafness with a cochlear implant (CI). This treatment represents a lifelong care process that requires continuous quality control over time. On the initiative of the Executive Committee of the German Society of Otorhinolaryngology (Deutsche Gesellschaft für Hals-Nasen-Ohren-Heilkunde, Kopf- und Hals-Chirurgie e.V., DGHNO-KHC), a national German CI registry (Deutsches Cochlear Implant Register, DCIR) was established in January 2022. This article focuses on the first demographic and baseline data of the DCIR.

Methods

The DCIR covers the complete therapeutic process from indication, surgery, fitting and lifelong aftercare in CI therapy. By the end of 2022, 75 hospitals in Germany had agreed to contribute to the DCIR.

Results

During the year 2022, 63 hospitals actively contributed data to the DCIR. Pseudonymized data from 2,292 CI implantations (2,176 primary implantations, 99 explantations with immediate re-implantations and 17 re-implantations following an earlier explantation) in 2,108 patients were documented. Cochlear implantation was accomplished in 1,807 adults (≥ 18 years) and 301 children (< 18 years). Fourty patients (1,9%) were children < 1 year of age and 55 (2,6%) were patients > 85 years. From the total of 2,292 implantations, 226 (9.9%) were performed as simultaneous bilateral implantations (CI implantation in both ears of 113 patients on the same day of surgery) and 412 implantations (19.1% of 2,162 implantations with data provided on the contralateral ear’s hearing status) were in patients with single sided deafness (normal hearing in the contralateral ear). In addition, the reported complications in 2022 were also evaluated. Seven reports (0.4%) of mild to moderate severe facial nerve dysfunctions were documented. No reports of severe or total facial nerve dysfunction (House-Brackmann grade V/VI), meningitis or death related to CI therapy were documented.

Conclusion

Although still in the start-up phase, these initial DCIR data already provide an interesting first insight into the demographic structure and baseline data of CI therapy in Germany. The successful implementation of the DCIR represents an important step towards continuous quality control of CI care.
Changes in paranasal sinus volumes, temporal bone pneumatization, internal acoustic canal and olfactory cleft dimensions over the centuries: a comparison of skulls from different epochs in Anatolia
Authors: Yücel Levent , Azizi Fatemeh , Meral Salih Cengiz , Sözer Çilem Sönmez , Erol Ayla Sevim , Çoşkun Zafer Ünsal , Gültekin Timur , Karaçaylı Ceren , Satar Bülent
Published: July 2024

Objectives

Investigating changes in temporal bone pneumatization (TBP) and paranasal sinus volumes (PSV) across different eras may help understanding not only changes in skull anatomy but also pathophysiology of chronic otitis media and sinusitis, respectively, which are common health problems.

Methods

Eight skulls from the second century AD, 20 skulls were from the 10th–11th centuries AD, 20 skulls from the 16th–19th centuries AD, and 60 contemporary skulls were included in this cross-sectional observational study. Using computerized tomography (CT) scans, the PSV were calculated by multiplying the height, width, and antero-posterior distance of the sinuses. TBP was divided into three types. Internal acoustic canal (IAC) length and width, and olfactory cleft (OC) width were measured.

Results

No statistically significant differences were found between the paranasal sinus (frontal, maxillary, and sphenoid) volumes between the groups. However, TBP decreased statistically significantly over time on both sides of the skulls (p = 0.001). The contemporary IAC and OC measures were found to be significantly lower on both sides compared to the skulls from the other three eras (p < 0.001 for both).

Conclusions

Although no significant change was observed in PSV, decreases were evident in TBP, OC width and IAC length and width over time. It appears a fair inference that changes in size of OC and IAC might be another indication of the fact that olfaction and hearing were more vital for survival in old eras. Since we do not know incidence of chronic ear problems in old eras, we cannot speculate outcome of increased TBP in terms of developing chronic ear diseases. On the contrary, increased TBP was likely to play a protective role in traumas in old ears. Additionally, the environmental influences may be crucial role in the development of paranasal sinuses.
Clinical spreading of muscle weakness in amyotrophic lateral sclerosis (ALS): a study in 910 patients
Authors: Ludolph Albert C. , Dietrich Jennifer , Dreyhaupt Jens , Kassubek Jan , Del Tredici Kelly , Rosenbohm Angela
Published: July 2024

Background

Neuroanatomical staging of sporadic amyotrophic lateral sclerosis (ALS) indicates that neurodegeneration may spread corticofugally.

Methods

We conducted an observational study to define the initial sites of disease onset and the clinical progression (‘spreading patterns’) of motor deficits in a cohort of 910 ALS patients in Germany.

Results

Mean age of ALS onset was 59.0 ± 12.6 years for males and 61.2 ± 10.5 years for females, the mean ALSFRS-R was 35.1 ± 9.2, and 7.7% of the cohort reported a family history. Onset of motor symptoms was bulbar/upper limb in 26.8%/35.9%, the right arm initially being slightly more often affected than the left (18.5% vs.16.3%). Testing on concordance of handedness and onset in the dominant arm did not reach significance. Lower limb onset was observed in 37.3%. Unilateral limb onset patients reported horizontal spreading about three times more often than vertical spreading. 71/244 bulbar onset patients reported spreading pattern to the legs, and 17/339 lumbar onset patients reported spreading secondarily to the bulbar region.

Discussion

Our results indicate that, although the phenotype of so-called ‘spinal’ or ‘intraspinal’ spreading predominated, we also observed an additional clinical spreading pattern: 29.1% of patients with bulbar onset experienced spreading clinically to the legs (vice versa in 5.0% of lumbar onset patients). For obvious neuroanatomical reasons, this pattern hardly can be explained solely by a ‘spinal’ or an ‘intraspinal’ pattern of spreading. Instead, these findings complement insights from previous clinical and clinicopathological studies supporting a cortical initiation of ALS.
The ethics of artificial intelligence systems in healthcare and medicine: from a local to a global perspective, and back
Authors: Vandemeulebroucke Tijs
Published: July 2024

Artificial intelligence systems (ai-systems) (e.g. machine learning, generative artificial intelligence), in healthcare and medicine, have been received with hopes of better care quality, more efficiency, lower care costs, etc. Simultaneously, these systems have been met with reservations regarding their impacts on stakeholders’ privacy, on changing power dynamics, on systemic biases, etc. Fortunately, healthcare and medicine have been guided by a multitude of ethical principles, frameworks, or approaches, which also guide the use of ai-systems in healthcare and medicine, in one form or another. Nevertheless, in this article, I argue that most of these approaches are inspired by a local isolationist view on ai-systems, here exemplified by the principlist approach. Despite positive contributions to laying out the ethical landscape of ai-systems in healthcare and medicine, such ethics approaches are too focused on a specific local healthcare and medical setting, be it a particular care relationship, a particular care organisation, or a particular society or region. By doing so, they lose sight of the global impacts ai-systems have, especially environmental impacts and related social impacts, such as increased health risks. To meet this gap, this article presents a global approach to the ethics of ai-systems in healthcare and medicine which consists of five levels of ethical impacts and analysis: individual-relational, organisational, societal, global, and historical. As such, this global approach incorporates the local isolationist view by integrating it in a wider landscape of ethical consideration so to ensure ai-systems meet the needs of everyone everywhere.
Fine mapping of candidate effector genes for heart rate
Authors: Ramírez Julia , van Duijvenboden Stefan , Young William J. , Chen Yutang , Usman Tania , Orini Michele , Lambiase Pier D. , Tinker Andrew , Bell Christopher G. , Morris Andrew P. , Munroe Patricia B.
Published: July 2024

An elevated resting heart rate (RHR) is associated with increased cardiovascular mortality. Genome-wide association studies (GWAS) have identified > 350 loci. Uniquely, in this study we applied genetic fine-mapping leveraging tissue specific chromatin segmentation and colocalization analyses to identify causal variants and candidate effector genes for RHR. We used RHR GWAS summary statistics from 388,237 individuals of European ancestry from UK Biobank and performed fine mapping using publicly available genomic annotation datasets. High-confidence causal variants (accounting for > 75% posterior probability) were identified, and we collated candidate effector genes using a multi-omics approach that combined evidence from colocalisation with molecular quantitative trait loci (QTLs), and long-range chromatin interaction analyses. Finally, we performed druggability analyses to investigate drug repurposing opportunities. The fine mapping pipeline indicated 442 distinct RHR signals. For 90 signals, a single variant was identified as a high-confidence causal variant, of which 22 were annotated as missense. In trait-relevant tissues, 39 signals colocalised with cis-expression QTLs (eQTLs), 3 with cis-protein QTLs (pQTLs), and 75 had promoter interactions via Hi-C. In total, 262 candidate genes were highlighted (79% had promoter interactions, 15% had a colocalised eQTL, 8% had a missense variant and 1% had a colocalised pQTL), and, for the first time, enrichment in nervous system pathways. Druggability analyses highlighted ACHE, CALCRL, MYT1 and TDP1 as potential targets. Our genetic fine-mapping pipeline prioritised 262 candidate genes for RHR that warrant further investigation in functional studies, and we provide potential therapeutic targets to reduce RHR and cardiovascular mortality.
Low-calorie diets are effective for weight loss in patients undergoing benign upper gastrointestinal surgery: a systematic review and meta-analysis
Authors: Chowdhury Nibir , Hasnan Syarafina , Ullah Shahid , Thompson Sarah K.
Published: July 2024

Background

Obesity may increase surgical complexity in patients undergoing abdominal surgery by limiting visualization and increasing the risk of peri-operative complications. A preoperative reduction in weight and liver volume may improve surgical outcomes. The aim of our study was to evaluate the efficacy of a low-calorie diet (LCD) versus a very low-calorie diet (VLCD) in reducing weight and liver volume prior to laparoscopic surgery.

Methods

A systematic search was conducted using the following inclusion criteria: obese patients undergoing preoperative weight loss using a VLCD or LCD, evaluation of liver volume reduction, and the use of an imaging modality before and after the diet.

Results

A total of 814 patients from 21 different studies were included in this systematic review and meta-analysis, with 544 female patients (66.8%) and a mean age range between 24 and 54 years old. There was a total mean weight loss of 6.42% and mean liver volume reduction of 16.7%. Meta-analysis demonstrated that a preoperative diet (LCD or VLCD) significantly reduced weight [SMD = − 0.68; 95% CI (− 0.93, − 0.42), I2 = 82%, p ≤ 0.01] and liver volume [SMD = − 2.03; 95% CI (− 4.00, − 0.06), I2 = 94%, p ≤ 0.01]. When assessed individually, a VLCD led to significant weight reduction [SMD = − 0.79; CI (− 1.24; − 0.34), p ≤ 0.01, I2 = 90%], as did an LCD [SMD = − 0.60; CI (− 0.90; − 0.29), p ≤ 0.01, I2 = 68%). Similarly, there was a significant reduction in liver volume following a VLCD [SMD = − 1.40; CI (− 2.77, − 0.03), p ≤ 0.01, I2 = 96%], and an LCD [SMD = − 2.66; CI (− 6.13, 0.81), p ≤ 0.01, I2 = 93%]. However, there was no significant difference between the two regimens.

Conclusions

Preoperative restrictive calorie diets are effective in reducing weight and liver volume prior to laparoscopic surgery. Whilst a VLCD was better than an LCD at reducing both weight and liver volume, the difference was not significant.

Graphical abstract
Responding to the workforce crisis: consensus recommendations from the Second Workforce Summit of the American Society of Pediatric Nephrology
Authors: Soranno Danielle E. , Amaral Sandra , Ashoor Isa , Atkinson Meredith A. , Barletta Gina-Marie , Braun Michael C. , Carlson Joann , Carter Caitlin , Chua Annabelle , Dharnidharka Vikas R. , Drake Keri , Erkan Elif , Feig Dan , Goldstein Stuart L. , Hains David , Harshman Lyndsay A. , Ingulli Elizabeth , Kula Alexander J. , Leonard Mary , Mannemuddhu Sudha , Menon Shina , Modi Zubin J. , Moxey-Mims Marva , Nada Arwa , Norwood Victoria , Starr Michelle C. , Verghese Priya S. , Weidemann Darcy , Weinstein Adam , Smith Jodi
Published: July 2024

Importance

Pediatric patients with complex medical problems benefit from pediatric sub-specialty care; however, a significant proportion of children live greater than 80 mi. away from pediatric sub-specialty care.

Objective

To identify current knowledge gaps and outline concrete next steps to make progress on issues that have persistently challenged the pediatric nephrology workforce.

Evidence review

Workforce Summit 2.0 employed the round table format and methodology for consensus building using adapted Delphi principles. Content domains were identified via input from the ASPN Workforce Committee, the ASPN’s 2023 Strategic Plan survey, the ASPN’s Pediatric Nephrology Division Directors survey, and ongoing feedback from ASPN members. Working groups met prior to the Summit to conduct an organized literature review and establish key questions to be addressed. The Summit was held in-person in November 2023. During the Summit, work groups presented their preliminary findings, and the at-large group developed the key action statements and future directions.

Findings

A holistic appraisal of the effort required to cover inpatient and outpatient sub-specialty care will help define faculty effort and time distribution. Most pediatric nephrologists practice in academic settings, so work beyond clinical care including education, research, advocacy, and administrative/service tasks may form a substantial amount of a faculty member’s time and effort. An academic relative value unit (RVU) may assist in creating a more inclusive assessment of their contributions to their academic practice. Pediatric sub-specialties, such as nephrology, contribute to the clinical mission and care of their institutions beyond their direct billable RVUs. Advocacy throughout the field of pediatrics is necessary in order for reimbursement of pediatric sub-specialist care to accurately reflect the time and effort required to address complex care needs. Flexible, individualized training pathways may improve recruitment into sub-specialty fields such as nephrology.

Conclusions and relevance

The workforce crisis facing the pediatric nephrology field is echoed throughout many pediatric sub-specialties. Efforts to improve recruitment, retention, and reimbursement are necessary to improve the care delivered to pediatric patients.

Graphical Abstract
Effect of Background Scattering on Efimov Scenario for Overlapping Narrow Feshbach Resonances
Authors: Hamodi-Gzal Fatema , Khaykovich Lev
Published: July 2024

Efimov physics in the vicinity of two overlapping narrow Feshbach resonances can be explored within a framework of a three-channel model where a non-interacting open channel is coupled to two closed molecular channels. Here, we determine how it compares to the extended two-channel model, which includes an open channel with finite background scattering and a single molecular channel. We identify the parameter range in which the three-channel model surpasses the extended two-channel model. Furthermore, the three-channel model is extended to include background scattering, and then both models are applied to the experimentally relevant system of bosonic lithium atoms polarized on two different energy levels, with an isolated and two overlapping narrow Feshbach resonances, respectively. We confirm, in agreement with previous studies, that being small, the background scattering length in lithium has a negligible effect on the Efimov features in the case of isolated resonance. However, in the case of overlapping Feshbach resonances, the inclusion of background scattering improves the performance of the theory with respect to the experimentally measured position of the Efimov resonance.