bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of peritoneal and wound lavage with super-oxidized solution on surgical-site infection after open appendicectomy in perforated appendicitis (PLaSSo): randomized clinical trial
Authors: Sellappan Harivinthan , Alagoo Dinesh , Loo Christina , Vijian Kaesarina , Sibin Rohamini , Chuah Jitt Aun
Published: October 2024

Background

Surgical-site infection following open appendicectomy for perforated appendicitis increases length of hospital stay and treatment costs while compromising patients’ quality of life. Data from randomized clinical trials (RCTs) evaluating the role of super-oxidized solution in perforated appendicitis are lacking. The study objective was to determine the effect of peritoneal and wound lavage with super-oxidized solution in reducing risk of surgical-site infection following open appendicectomy for perforated appendicitis.

Methods

In this multicentre RCT conducted between September 2020 and March 2022, patients aged 13 years and older with perforated appendicitis undergoing open appendicectomy were randomly assigned to receive peritoneal and wound lavage with either super-oxidized solution or normal saline. The primary outcome was surgical-site infection within 30 days after surgery. Randomization was computer-generated, with allocation concealment by opaque, sequentially numbered, sealed envelope. The patients, surgeons, outcome assessors and statisticians performing the analysis were blinded to treatment assigned.

Results

A total of 102 consecutive patients (51 in the super-oxidized solution group and 51 in the normal saline group) were randomized and included in the intention-to-treat analysis. The super-oxidized solution group showed a significant reduction in overall surgical-site infection (8 (15.6%) versus 19 (37.2%); relative risk (RR) 0.42; 95% c.i. 0.20 to 0.87; P = 0.014), and superficial surgical-site infection (5 (9.8%) versus 18 (35.3%); RR 0.28; 95% c.i. 0.11 to 0.69; P = 0.002), with a number-needed-to-treat of four patients. There were no adverse events in either group.

Conclusions

Peritoneal and wound lavage with super-oxidized solution is superior to normal saline in preventing surgical-site infection after open appendicectomy for perforated appendicitis.

Trial Registration

ClinicalTrial.gov Identifier: NCT04512196
Direct quotations in social work writing: multi-functionality and double voicing
Authors: Leedham Maria , Lillis Theresa , Twiner Alison
Published: October 2024

Writing comprises a core area of social work as a substantial amount of time is spent on producing case notes, assessment reports, and other required documentation in order to progress cases; however, little research has been carried out on social workers’ writing and, in particular, the specific discursive and rhetorical devices employed to create effective texts. One rhetorical device often employed in order to include the voices of service users and their families is the use of quotations. This article explores the extent to which quotations are used across social work domains and text types, the different voices represented through quotations, and the perceived functions of the quotations. The study draws on three different data types: (1) a 1-million-word corpus of social workers’ writing; (2) social worker interviews (n = 81); (3) two case studies comprising texts, interviews with the social worker writer, and researcher observations. All data were collected within the WiSP project and were interrogated through a mix of computational and qualitative analysis to develop a taxonomy of functions of quotations. In addition to furthering our understanding of how quotations are employed in professional writing, the study has implications for social worker training and practice.
The clinical and genetic spectrum of paediatric speech and language disorders
Authors: Magielski Jan H , Ruggiero Sarah M , Xian Julie , Parthasarathy Shridhar , Galer Peter D , Ganesan Shiva , Back Amanda , McKee Jillian L , McSalley Ian , Gonzalez Alexander K , Morgan Angela , Donaher Joseph , Helbig Ingo
Published: October 2024

Speech and language disorders are known to have a substantial genetic contribution. Although frequently examined as components of other conditions, research on the genetic basis of linguistic differences as separate phenotypic subgroups has been limited so far.

Here, we performed an in-depth characterization of speech and language disorders in 52 143 individuals, reconstructing clinical histories using a large-scale data-mining approach of the electronic medical records from an entire large paediatric healthcare network.

The reported frequency of these disorders was the highest between 2 and 5 years old and spanned a spectrum of 26 broad speech and language diagnoses. We used natural language processing to assess the degree to which clinical diagnoses in full-text notes were reflected in ICD-10 diagnosis codes. We found that aphasia and speech apraxia could be retrieved easily through ICD-10 diagnosis codes, whereas stuttering as a speech phenotype was coded in only 12% of individuals through appropriate ICD-10 codes. We found significant comorbidity of speech and language disorders in neurodevelopmental conditions (30.31%) and, to a lesser degree, with epilepsies (6.07%) and movement disorders (2.05%). The most common genetic disorders retrievable in our analysis of electronic medical records were STXBP1 (n = 21), PTEN (n = 20) and CACNA1A (n = 18). When assessing associations of genetic diagnoses with specific linguistic phenotypes, we observed associations of STXBP1 and aphasia (P = 8.57 × 10−7, 95% confidence interval = 18.62–130.39) and MYO7A with speech and language development delay attributable to hearing loss (P = 1.24 × 10−5, 95% confidence interval = 17.46–infinity). Finally, in a sub-cohort of 726 individuals with whole-exome sequencing data, we identified an enrichment of rare variants in neuronal receptor pathways, in addition to associations of UQCRC1 and KIF17 with expressive aphasia, MROH8 and BCHE with poor speech, and USP37, SLC22A9 and UMODL1 with aphasia.

In summary, our study outlines the landscape of paediatric speech and language disorders, confirming the phenotypic complexity of linguistic traits and novel genotype–phenotype associations. Subgroups of paediatric speech and language disorders differ significantly with respect to the composition of monogenic aetiologies.
Default mode network tau predicts future clinical decline in atypical early Alzheimer’s disease
Authors: Katsumi Yuta , Howe Inola A , Eckbo Ryan , Wong Bonnie , Quimby Megan , Hochberg Daisy , McGinnis Scott M , Putcha Deepti , Wolk David A , Touroutoglou Alexandra , Dickerson Bradford C
Published: October 2024

Identifying individuals with early-stage Alzheimer’s disease (AD) at greater risk of steeper clinical decline would enable better-informed medical, support and life planning decisions. Despite accumulating evidence on the clinical prognostic value of tau PET in typical late-onset amnestic AD, its utility in predicting clinical decline in individuals with atypical forms of AD remains unclear. Across heterogeneous clinical phenotypes, patients with atypical AD consistently exhibit abnormal tau accumulation in the posterior nodes of the default mode network of the cerebral cortex. This evidence suggests that tau burden in this functional network could be a common imaging biomarker for prognostication across the syndromic spectrum of AD.

Here, we examined the relationship between baseline tau PET signal and the rate of subsequent clinical decline in a sample of 48 A+/T+/N+ patients with mild cognitive impairment or mild dementia due to AD with atypical clinical phenotypes: Posterior Cortical Atrophy (n = 16); logopenic variant Primary Progressive Aphasia (n = 15); and amnestic syndrome with multi-domain impairment and young age of onset < 65 years (n = 17). All patients underwent MRI, tau PET and amyloid PET scans at baseline. Each patient’s longitudinal clinical decline was assessed by calculating the annualized change in the Clinical Dementia Rating Sum-of-Boxes (CDR-SB) scores from baseline to follow-up (mean time interval = 14.55 ± 3.97 months).

Atypical early AD patients showed an increase in CDR-SB by 1.18 ± 1.25 points per year: t(47) = 6.56, P < 0.001, Cohen’s d = 0.95. Across clinical phenotypes, baseline tau in the default mode network was the strongest predictor of clinical decline (R2 = 0.30), outperforming a simpler model with baseline clinical impairment and demographic variables (R2 = 0.10), tau in other functional networks (R2 = 0.11–0.26) and the magnitude of cortical atrophy (R2 = 0.20) and amyloid burden (R2 = 0.09) in the default mode network.

Overall, these findings point to the contribution of default mode network tau to predicting the magnitude of clinical decline in atypical early AD patients 1 year later. This simple measure could aid the development of a personalized prognostic, monitoring and treatment plan, which would help clinicians not only predict the natural evolution of the disease but also estimate the effect of disease-modifying therapies on slowing subsequent clinical decline given the patient’s tau burden while still early in the disease course.
Innovations and challenges in predicting cognitive trajectories after stroke
Authors: Demeyere Nele , Moore Margaret J
Published: October 2024

This scientific commentary refers to ‘Deep learning disconnectomes to accelerate and improve long-term predictions for post-stroke symptoms’, by Matsulevits et al. (https://doi.org/10.1093/braincomms/fcae338).
Integrated Two Step Co-Pyrolysis Under Several Low-Cost Natural Catalyst to Produce of Aromatic-Rich Liquid Fuel from Mixed Municipal Solid Waste
Authors: Gandidi Indra Mamad , Sukrawan Y , Kuntadi Iwa , Pambudi Nugroho Agung , Hamni Arinal
Published: October 2024

The world's increasing human population and industrial activities have resulted in an enormous rise in energy consumption throughout the years. A severe attention has developed regarding an impending energy crisis caused by the depletion of fossil fuel supplies and their contribution to environmental degradation. As a result, it is necessary to investigate and make use of non-fossil energy sources for the purpose of maintaining demand stability as well as creating a sustainable green environment. Pyrolysis is a reliable method to convert materials from municipal solid waste to useful energy. Hence, the co-pyrolysis of unsegregated municipal solid waste was investigated in this study using an integrated two-step pyrolysis by double reactor that was supported by various natural catalysts such as zeolite, dolomite, and kaolin at 550 °C for 210 minutes as constant variables in which it has not been reported previously. To obtain the physical and chemical properties, liquid fuel was subjected to ASTM and gas chromatography-mass spectroscopy analyses and examining the impact of each catalyst on its characteristics. The aromatic fraction was prominent in the liquid fuel yields produced by kaolin and zeolite catalysts (57.4 and 46.1% peak area, respectively). Meanwhile, the greatest liquid fuel was produced by using dolomite as catalyst. The viscosity and density of liquid fuel with dolomite, kaolin, and zeolite were 10.83, 4.25, and 4.04 mm2/s and 0.88, 0.89, and 1.01 g/cm3, respectively. Conversely, the corresponding calorific values for zeolite, kaolin, and dolomite are 41.37, 41.09, and 41.19 MJ/kg. Its physical characteristics are comparable to those of common fuels like petrol-88, which was utilized in Indonesia as a vehicle fuel.
Inborn errors of immunity-related immunological mechanisms and pharmacological therapy alternatives in periodontitis
Authors: Nabiyeva Çevik Nadira , Berker Ezel , Tezcan Ilhan , Cagdas Deniz
Published: October 2024

Periodontitis is a frequent local inflammatory disease. The microbiota and repeated exposure to bacterial endotoxins triggers excessive inflammation through oral mucosal immunity and sometimes leads to a destructive effect on the supportive mucosal tissues around the teeth. Elimination of the pathogens and increasing the tolerance of the cellular immune response is crucial in addition to standard dental therapies like mechanical debridement. Based on our experience with immune-mediated diseases, especially primary immunodeficiency diseases, we wrote this review to discuss the treatment alternatives for severe periodontal disease. Risk factors are malnutrition, vitamin deficiencies, smoking, systemic inherited and acquired immune-mediated diseases, infections, endocrinological diseases, and pharmacological agents that may accompany periodontitis. The diagnosis and treatment of dietary deficiencies, as well as the addition of nutritional supplements, may aid in epithelial regeneration and immune system function. Recently, modifications to the therapeutic option for severe periodontitis have been made depending on the fact that the immune response against bacteria may modify the severity of periodontal inflammation. The anti-inflammatory therapies support or inhibit the host’s immune response. The clinical approach to severe periodontitis should extend beyond classical therapies. There is a need for a diverse therapeutic strategy that supports the epithelial barrier, which is the crucial component of innate immunity against microbiota. Leukocytes are the main cellular component in periodontal inflammation. Anti-inflammatory therapeutic options directed at leukocytes, such as IL-17 and IL-23-targeted therapies, could be the candidates for the treatment of severe periodontitis. Therapy against other inflammatory cytokines, IL-1, IL-6, IL-12, IL-23, TNF-alpha, PGE2, and cytokine receptors, could also be used in periodontal inflammation control.
Changes in 24-hour blood pressure profile after 12 weeks of dapagliflozin treatment in patients with diabetic kidney disease: an Italian multicenter prospective study
Authors: Borrelli Silvio , Garofalo Carlo , Reboldi Gianpaolo , Coppola Annapaola , Chiodini Paolo , Simeoni Mariadelina , Mazzieri Alessio , della Volpe Luca , Gallieni Maurizio , Zummo Carola , Cottone Santina , Ravera Maura , Aucella Filippo , Aucella Francesco , Stallone Giovanni , Gismondi Valeria , Alberici Federico , Gregori Marco , Castellano Giuseppe , Vettoretti Simone , Cozzolino Mario , Ruotolo Chiara , Minutolo Roberto , De Nicola Luca
Published: October 2024

Background

Sodium-glucose cotransporter 2 inhibitors (SGLT2i) lower ambulatory blood pressure (ABP) in patients with type 2 diabetes mellitus; whether the same holds true in diabetic kidney disease (DKD) is unknown. This information is critical to the knowledge of mechanisms of nephroprotection and safety of this therapy.

Methods

This multicenter prospective study evaluates the changes in ABP after 12 weeks of dapagliflozin 10 mg/day in a cohort of patients with type 2 DKD and glomerular filtration rate (GFR) >25 mL/min/1.73 m2. Primary endpoint was the change of nighttime systolic blood pressure (SBP). Changes of daytime SBP, prevalence of normal dipping (day/night SBP ratio <0.9) and changes in ABP patterns, that is, sustained uncontrolled hypertension (SUCH), white coat uncontrolled hypertension (WUCH), masked uncontrolled hypertension (MUCH) and controlled hypertension (CH) were secondary endpoints.

Results

Eighty-three of 96 patients completed the study [age 68.7 ± 8.9 years, 73.5% males, GFR 49 ± 17 mL/min/1.73 m2, median albuminuria: 0.18 (interquartile range 0.10–0.38) g/24 h]. After 12 weeks of dapagliflozin, nighttime SBP declined by −3.0 mmHg (95% confidence interval −5.2/−0.8 mmHg; P = .010) with an improvement of nighttime SBP goal (<110 mmHg) from 18.0% to 27.0% (P < .001). Similarly, the prevalence of normal dipping increased (from 31.3% to 50.6%, P = .005). A decrease in daytime (−2.4 mmHg; P = .046) and office (−7.9 mmHg; P = .009) SBP was also found. The decline of ambulatory and office SBP was associated with increased prevalence of CH (from 6.0% to 18.0%) and significant improvement of SUCH, WUCH and MUCH (P = .009). Albuminuria decreased (P < .001), whereas eGFR did not change (P = .297). Urinary tract infection (4.2%) and acute kidney injury (3.6%) were the main causes of drop-out. Only one patient showed a drop of nighttime SBP below 90 mmHg.

Conclusions

Dapagliflozin is associated with improvement in circadian blood pressure rhythm with no major safety signal related to excessive blood pressure decrease.
Particle swarm optimization method applied in total life cycle materials allocation of electricity engineering projects in the green and low-carbon supply chain
Authors: Si Jiandong , Shao Xuwei , Wu Jianfeng , Zhao Xin , Ye Weijing , Wang Jing
Published: October 2024

Power grid enterprises face the problem of unbalanced supply and demand of power materials and unequal distribution; intelligent allocation of power materials can optimize the distribution and use of power resources through advanced technology and algorithms to ensure the efficient use of energy and stable supply. In this paper, the whole life cycle cost model of power supply chain is constructed and solved by improved particle swarm optimization (PSO). This algorithm combines the advantages of standard PSO and genetic algorithm (GA), avoids their disadvantages effectively, and realizes the effect of complementary advantages. This paper proposes using the sum of the costs associated with warehousing, transportation, and service penalties in the supply chain of electrical power projects as the objective function, thereby achieving the goal of optimal supply chain costs. In this study, the improved PSO algorithm is used to optimize the objective function, and the optimization results are compared with those of standard PSO algorithm and GA, revealing that its convergence is superior to the other two algorithms. Considering the influence of different factors on the cost, the superiority of the improved PSO algorithm is further verified.
Assessing indoor air quality and health risks of air conditioner usage in residential buildings under hot and arid climatic conditions: insights from field studies and questionnaire analysis
Authors: Benyamine Mébirika , Fezzioui Naïma , Alkhafaji Mohammed Ayad , Kaid Noureddine , Benti Natei Ermias , Menni Younes
Published: October 2024

The prevalence of air conditioners (ACs) in regions with hot and arid climates raises significant health concerns for users. This study investigates the impact of AC usage on health and indoor air quality in Kenadsa, Bechar, located in southwest Algeria. A questionnaire survey was conducted among 300 residents to identify symptoms associated with AC use. Additionally, dust accumulation in filters was measured in 20 households with varying occupancy types to assess the relationship between particle generation and room usage. Temperature and relative humidity were also recorded in two rooms, one equipped with an evaporative cooler and the other with a split-type AC, to compare their thermal performance. The findings reveal that occupant behavior and building usage significantly contribute to particle generation, with AC operating speed notably impacting filter contamination. Evaporative coolers increase temperature and humidity levels compared to split-type ACs, with their effectiveness depending on proper ventilation. Most respondents begin using ACs in May, prefer operating them during midday and nighttime, and express concerns about thermal shock and AC lifespan. Furthermore, many participants are lax in dust removal, potentially worsening indoor air pollution. A significant portion of respondents report various health issues linked to prolonged exposure to conditioned air but show limited awareness of AC filter maintenance and its health implications. This study highlights the complex interplay between human behavior, AC usage patterns, and indoor air quality, emphasizing the need for targeted interventions to promote responsible AC use, improve filter maintenance practices, and mitigate associated health risks in hot and dry climates.
Next-Generation SARS-CoV-2 Vaccine Formulations and Alternative Routes of Administration
Authors: Babu Tara M , Jackson Lisa A , El Sahly Hana M
Published: October 2024

The development of SARS-CoV-2 next-generation vaccines with the potential for increased effectiveness, durability, breadth, and ability to decrease transmission are of public health importance. We highlight alternative routes of administration of next-generation SARS-CoV-2 vaccines such as mucosal and intradermal administration.
Social and Environmental Benefits of Pediatric Infectious Disease Telemedicine
Authors: Lu Lydia S , Dalby Allyson , Jaggi Preeti , Fox Thomas G
Published: October 2024

We provided safe, effective pediatric infectious disease management through telemedicine over a 3.5-year period, saving patients over 31 000 vehicular travel miles. Telemedicine has potential to decrease indirect patient costs while sustainably increasing access to subspecialty care.
Dosimetric commissioning of a high-resolution CMOS 2D detector array for patient-specific QA of single-isocenter multi-target VMAT stereotactic radiosurgery
Authors: Teng Ching-Ling , Lin Shih-Chi , Lovelock Dale Michael , Lim Seng Boh
Published: October 2024

Stereotactic radiosurgery (SRS) using the single-isocenter-multiple-target (SIMT) technique by volumetric modulated arc therapy is increasingly popular for treating multiple brain metastases. However, the complex nature of SIMT SRS necessitates rigorous patient-specific quality assurance (PSQA). This study presents a multi-institutional dosimetric commissioning of a high-resolution complementary metal oxide semiconductor (CMOS) 2D detector array, the myQA SRS device for SIMT SRS PSQA. Basic dosimetric properties such as dose-rate, field-size, energy and angular dependencies were characterized for the CMOS detectors. Additionally, gamma index analyses were performed between the measured dose and the films for nine simulated and clinical plans. The results showed that the CMOS detector was dose-rate, field-size, energy and beam-angle dependent. Specific to SIMT SRS, angular dependence on gantry rotations was invariant to couch rotations but was sensitive to off-isocenter distances. With appropriate dose calibration and angular corrections, myQA SRS showed a high dosimetric correlation with films. The average gamma index pass rates were 99.9 ± 0.03% and 99.2 ± 1.1% at 3%/2 mm/10%thr(global) and 1 mm/1%/10%thr(local) criteria, respectively. The average dose difference between myQA SRS and films was 0.4 ± 1.3%. In conclusion, the CMOS 2D detector array has demonstrated its potential as a reliable tool for PSQA for SIMT SRS. The excellent dosimetric agreement with the films was consistent in multiple institutions, further validating the dosimetric accuracy and reproducibility. It provides a timely alternative to film dosimetry for commissioning and quality assurance.
Massively parallel binding assay (MPBA) reveals limited transcription factor binding cooperativity, challenging models of specificity
Authors: Jana Lang Tamar , Brodsky Sagie , Manadre Wajd , Vidavski Matan , Valinsky Gili , Mindel Vladimir , Ilan Guy , Carmi Miri , Jonas Felix , Barkai Naama
Published: October 2024

DNA-binding domains (DBDs) within transcription factors (TFs) recognize short sequence motifs that are highly abundant in genomes. In vivo, TFs bind only a small subset of motif occurrences, which is often attributed to the cooperative binding of interacting TFs at proximal motifs. However, large-scale testing of this model is still lacking. Here, we describe a novel method allowing parallel measurement of TF binding to thousands of designed sequences within yeast cells and apply it to quantify the binding of dozens of TFs to libraries of regulatory regions containing clusters of binding motifs, systematically mutating all motif combinations. With few exceptions, TF occupancies were well explained by independent binding to individual motifs, with motif cooperation being of only limited effects. Our results challenge the general role of motif combinatorics in directing TF genomic binding and open new avenues for exploring the basis of protein–DNA interactions within cells.
Core enhancers of the 3′RR optimize IgH nuclear position and loop conformation for successful oriented class switch recombination
Authors: Bruzeau Charlotte , Martin Ophélie , Pollet Justine , Thomas Morgane , Ba Zhaoqing , Roulois David , Pinaud Eric , Le Noir Sandrine
Published: October 2024

In B lymphocytes, class switch recombination (CSR) is an essential process that adapts immunoglobulin (Ig) subtypes to antigen response. Taking place within the Ig heavy chain (IgH) locus, CSR needs controlled transcription of targeted regions governed by the IgH 3′ regulatory region (3′RR). This super-enhancer is composed of four core enhancers surrounded by inverted repeated sequences, forming a quasi-palindrome. In addition to transcription, nuclear organization appears to be an important level in CSR regulation. While it is now established that chromatin loop extrusion takes place within IgH locus to facilitate CSR by bringing the donor and acceptor switch regions closer together, the underlying mechanism that triggers CSR loop formation remains partially understood. Here, by combining DNA 3D fluorescence in situhybridization with various high-throughput approaches, we deciphered critical functions for the 3′RR core enhancer element in nuclear addressing, accessibility and chromatin looping of the IgH locus. We conclude that the 3′RR core enhancers are necessary and sufficient to pre-organize the position and conformation of IgH loci in resting B-cell nuclei to enable the deletional recombination events required for productive successful CSR in activated B-cell nuclei.
Various plasmid strategies limit the effect of bacterial restriction–modification systems against conjugation
Authors: Dimitriu Tatiana , Szczelkun Mark D , Westra Edze R
Published: October 2024

In bacteria, genes conferring antibiotic resistance are mostly carried on conjugative plasmids, mobile genetic elements that spread horizontally between bacterial hosts. Bacteria carry defence systems that defend them against genetic parasites, but how effective these are against plasmid conjugation is poorly understood. Here, we study to what extent restriction–modification (RM) systems—by far the most prevalent bacterial defence systems—act as a barrier against plasmids. Using 10 different RM systems and 13 natural plasmids conferring antibiotic resistance in Escherichia coli, we uncovered variation in defence efficiency ranging from none to 105-fold protection. Further analysis revealed genetic features of plasmids that explain the observed variation in defence levels. First, the number of RM recognition sites present on the plasmids generally correlates with defence levels, with higher numbers of sites being associated with stronger defence. Second, some plasmids encode methylases that protect against restriction activity. Finally, we show that a high number of plasmids in our collection encode anti-restriction genes that provide protection against several types of RM systems. Overall, our results show that it is common for plasmids to encode anti-RM strategies, and that, as a consequence, RM systems form only a weak barrier for plasmid transfer by conjugation.
Van der Waals epitaxial growth of single-crystal molecular film
Authors: Liu Lixin , Gong Penglai , Liu Kailang , Huang Bingrong , Zhang Zhihao , Fu Yingshuang , Wu Yu , Zhao Yinghe , Wang Meihui , Xu Yongshan , Li Huiqiao , Zhai Tianyou
Published: October 2024

Epitaxy is the cornerstone of semiconductor technology, enabling the fabrication of single-crystal film. Recent advancements in van der Waals (vdW) epitaxy have opened new avenues for producing wafer-scale single-crystal 2D atomic crystals. However, when it comes to molecular crystals, the overall weak vdW force means that it is a significant challenge for small molecules to form a well-ordered structure during epitaxy. Here we demonstrate that the vdW epitaxy of Sb2O3 molecular crystal, where the whole growth process is governed by vdW interactions, can be precisely controlled. The nucleation is deterministically modulated by epilayer–substrate interactions and unidirectional nuclei are realized through designing the lattice and symmetry matching between epilayer and substrate. Moreover, the growth and coalescence of nuclei as well as the layer-by-layer growth mode are kinetically realized via tackling the Schwoebel-Ehrlich barrier. Such precise control of vdW epitaxy enables the growth of single-crystal Sb2O3 molecular film with desirable thickness. Using the ultrathin highly oriented Sb2O3 film as a gate dielectric, we fabricated MoS2-based field-effect transistors that exhibit superior device performance. The results substantiate the viability of precisely managing molecule alignment in vdW epitaxy, paving the way for large-scale synthesis of single-crystal 2D molecular crystals.
Cosolvent electrolyte chemistries for high-voltage potassium-ion battery
Authors: Shen Mengkang , Dai Zhongqin , Fan Ling , Fu Hongwei , Geng Yuanhui , Guan Jie , Sun Fanfei , Rao Apparao M , Zhou Jiang , Lu Bingan
Published: October 2024

The poor oxidation resistance of traditional electrolytes has hampered the development of high-voltage potassium-ion battery technology. Here, we present a cosolvent electrolyte design strategy to overcome the high-voltage limitations of potassium-ion electrolyte chemistries. The cosolvent electrolyte breaks the dissolution limitation of the salt through ion–dipole interactions, significantly enlarging the anion-rich solvation clusters, as verified by the insitu synchrotron-based wide-angle X-ray scattering experiments. Furthermore, the large anion-rich solvation clusters also facilitate the formation of an effective electrode–electrolyte interphase, thereby enhancing compatibility with high-voltage electrodes. The cosolvent electrolyte enables K||Prussian blue cells (2–4.5 V) to operate for >700 cycles with a capacity retention of 91.9%. Our cosolvent electrolyte design strategy paves new avenues for the development of high-voltage potassium-ion batteries and beyond.
Preclinical Evidence of the Effects of Sweet Flavors: Sweetness Increases Nicotine Intake and Seeking
Authors: Bagdas Deniz , Addy Nii A
Published: October 2024

Introduction

The influence of early exposure to sweet and fruit flavors on subsequent nicotine use behaviors during adolescence remains poorly understood. To address this gap, we utilized a rodent model to simulate childhood flavor exposure and examine its effects on later nicotine use behaviors.

Aims and Methods

We employed a two-bottle choice paradigm in weanling rats to mimic human childhood flavor exposure. Subsequently, we investigated the impact of early exposure to sweet (saccharin) and cherry fruit (benzaldehyde) flavors on adolescent nicotine use behaviors. This included assessing subsequent nicotine acquisition, maintenance, and seeking behaviors using intraoral flavor and intravenous nicotine self-administration.

Results

Our findings reveal that rats exposed to saccharin during early development exhibited altered patterns of nicotine intake and seeking behaviors during adolescence. Specifically, rats demonstrated increased nicotine intake and seeking of saccharin flavored solutions when paired with nicotine, indicating a potential predisposition towards nicotine use following childhood flavor exposure. Intraoral benzaldehyde did not affect nicotine reinforcement in early sessions of self-administration, but significantly decreased nicotine reinforcement during later sessions. Both saccharin exposure alone or in combination with benzaldehyde promoted nicotine reinforcement. No significant sex differences in nicotine-related behaviors were observed.

Conclusions

This study highlights the significance of early flavor exposure in shaping adolescent nicotine use behaviors. The findings suggest that childhood exposure to sweet flavors may contribute to heightened susceptibility to nicotine use and addiction later in life. Understanding these early influences is crucial for developing targeted interventions to prevent the onset of nicotine addiction during adolescence.

Implications

Our study highlights the importance of how sweetness can contribute to and possibly even alter the effects of the flavor itself. The sweetness of a tobacco product does not solely stem from sweeteners, but it is also influenced by other components such as the propylene glycol (PG) and vegetable glycerin (VG) ratio (eg, higher VG) and the inclusion of flavors associated with sweetness (eg, vanillin and ethyl maltol). Therefore, sweet-associated constituents in tobacco products should be investigated further to inform regulatory policy. We believe that our findings can inform regulatory decisions on controlling sweet-associated constituents in tobacco products.
A Pumpless and Tubeless Microfluidic Device Enables Extended In Vitro Development of Cryptosporidium parvum
Authors: Gunasekera Samantha , Thierry Benjamin , Cheah Edward , King Brendon , Monis Paul , Carr Jillian M , Chopra Abha , Watson Mark , O’Dea Mark , Ryan Una
Published: October 2024

Background

The enteric parasite Cryptosporidium remains a treatment challenge for drinking water utilities globally due to its resistance to chlorine disinfection. However, the lack of an in vitro culture system for Cryptosporidium that is both cost-effective and reliable remains a key bottleneck in Cryptosporidium research.

Methods

Here we report that the microfluidic culture of human ileocecal colorectal adenocarcinoma (HCT-8) cells under fluid shear stress enables the extended development of Cryptosporidium parvum. Specifically, the growth of C. parvum in a user-friendly pumpless microfluidic device was assessed using immunofluorescence assays, scanning electron microscopy, and quantitative polymerase chain reaction, which revealed that development continued for 10 days in total.

Results

Oocysts produced within the microfluidic device were infective to fresh HCT-8 monolayers; however, these oocysts were only present at low levels.

Conclusions

We anticipate that such microfluidic approaches will facilitate a wide range of in vitro studies on Cryptosporidium and may have the potential to be further developed as a routine infectivity assessment tool for the water industry.
Enhancers in Plant Development, Adaptation and Evolution
Authors: Beernink Bliss M , Vogel John P , Lei Li
Published: October 2024

Understanding plant responses to developmental and environmental cues is crucial for studying morphological divergence and local adaptation. Gene expression changes, governed by cis-regulatory modules (CRMs) including enhancers, are a major source of plant phenotypic variation. However, while genome-wide approaches have revealed thousands of putative enhancers in mammals, far fewer have been identified and functionally characterized in plants. This review provides an overview of how enhancers function to control gene regulation, methods to predict DNA sequences that may have enhancer activity, methods utilized to functionally validate enhancers and the current knowledge of enhancers in plants, including how they impact plant development, response to environment and evolutionary adaptation.
Prevalence and associated risk factors of myocardial ischemia in children living with sickle cell anemia in Lagos, Nigeria
Authors: Adeniyi Oluwatoyin , Salako Abideen , Sokunbi Ogochukwu , Odubela Oluwatosin , Aworanti Oladapo , Okoromah Christy , Akinsulie Adebola
Published: October 2024

Myocardial ischemia (MI) in children living with sickle cell anemia (SCA) is rarely reported. MI among children living with this disease could portend untoward outcomes on their quality of life and survival. This study evaluated the prevalence and associated risk factors of MI in children living with SCA during a vaso-occlusive crisis (VOC) compared with those with SCA who had no symptoms nor an MI in the past (those in “steady state”) in Lagos, Nigeria. This comparative cross-sectional study was conducted over 10 months (between March and December 2019) among 250 children living with SCA aged 6 months–18 years (125 in VOC and 125 age and sex-matched controls in steady state). The assessment of MI was determined by measuring cardiac troponin T (cTnT) and electrocardiography (ECG). The prevalence of MI measuring cTnT alone in children with SCA during VOC and steady state was 42.4% and 23.2%, respectively. Comparatively, measuring ECG alone, the prevalence of MI in VOC and steady state was 40.8% and 20.8%, respectively. The prevalence of MI measuring cTnT and ECG in children with SCA in VOC and steady state was 38.4% and 20%, respectively. Older age, severity of pain, longer duration of illness, frequent crises per year, elevated white blood cells, and platelet count were significantly associated with MI in participants with SCA. However, with multivariate analysis, age, severity of pain, and elevated platelet counts remained significantly associated with the occurrence of MI. This study affirms the high prevalence of MI in children with SCA irrespective of the diagnostic criteria. Routine evaluation should be done in this cohort to avert MI-associated sequelae.
Styles, strategies, and challenges of PA leaders nationally
Authors: Grubb Bethany
Published: October 2024

Objectives:

To identify the leadership styles, strengths, strategies, and key factors of PA leaders in healthcare executive, clinical, and academic settings.

Methods:

An exploratory, qualitative study was completed through the American Academy of Physician Associates 2023 Practice Survey to answer seven qualitative questions. Of the 1,423 PAs who responded to the survey invitation, 348 PA leaders in formal and informal roles chose to answer, for a 24.4% response rate.

Results:

For PA leaders' styles and strengths, collaborative and emotional intelligence emerged as themes. For key factors of PA leadership, balancing expectations and giving and receiving critical feedback emerged as themes. For skills or qualities PA leaders wish they had before starting to lead, project management skills and increased confidence emerged as themes.

Conclusions:

Leadership development training needs to be in the didactic and clinical curriculum of PA programs for the future of PA leadership. Leadership pathways for PA leaders in healthcare executive, clinical, and academic settings need to be created and established more widely.
Mismatch Repair Status and Surgical Outcomes in Localized Colorectal Cancer: A Nationwide Cohort Study
Authors: Justesen Tobias Freyberg , Orhan Adile , Rosen Andreas Weinberger , Gögenur Mikail , Gögenur Ismail
Published: October 2024

Objective:

This study examined the association between deficient mismatch repair (dMMR) versus proficient MMR (pMMR) status and overall survival and disease-free survival in patients with localized colorectal cancer.

Background:

Several distinctions exist between patients with dMMR and pMMR colorectal cancer. However, the impact on prognosis is yet to be investigated in large-scale cohort studies.

Methods:

In this cohort study, we included patients who underwent curative-intent surgery for localized colorectal cancer between 2009 and 2020. Patients were identified in the Danish Colorectal Cancer Group database and patient-level data were extracted from 6 registry databases. After inclusion, patients with dMMR status were matched 1:1 to patients with pMMR status using an estimated propensity score.

Results:

After matching, 5994 patients were included. The patients had a median age of 74 years and a median follow-up of 4.1 years. There was no significant association between mismatch repair (MMR) status and overall survival (hazard ratio, 0.91; 95% confidence interval [CI], 0.81–1.03) or disease-free survival (hazard ratio, 0.89; 95% CI, 0.78–1.01). However, the restricted 5-year mean disease-free survival time, calculated due to violation of the proportional hazards assumption, showed a significant absolute difference of 0.13 years (95% CI, 0.03–0.23; P = 0.01) in favor of the dMMR group.

Conclusions:

No significant association with overall survival was found according to MMR status. dMMR status was, however, found to be associated with marginally improved disease-free survival compared to pMMR status in patients with localized colorectal cancer undergoing curative-intent surgery.
A Variable-Stimulus Distortion Product Otoacoustic Emission Screening Method to Match Cochlear Place-Specific Properties
Authors: Stiepan Samantha , Dhar Sumitrajit
Published: October 2024

Objectives:

Distortion product otoacoustic emissions (DPOAEs) are a popular screening tool for hearing loss in specific populations (e.g., newborns). Current screening protocols use stimulus conditions that are agnostic to local mechanical properties of the cochlea and are also limited to a narrow frequency range. We have recently reported locally optimized stimulus frequency ratio and level combinations for recording DPOAEs up to stimulus frequencies of 19 kHz. In normally functioning cochlea, optimized stimuli improved the signal to noise ratios and allowed the registration of higher DPOAE levels, especially at higher frequencies. The purpose of this study was to evaluate the clinical performance of these physiologically motivated, locally appropriate, stimulus parameters for a screening application to identify the presence of hearing loss.

Design:

Subjects were 24 adults with sensorineural hearing loss and 31 adults with normal hearing. The cubic DPOAE was measured and analyzed up to frequencies of 16 kHz using a range of stimulus conditions. Receiver operating characteristic curves were used to identify stimulus combinations most sensitive to screening for hearing loss.

Results:

Receiver operating characteristic curves demonstrated improved test efficacy for hearing loss detection when using stimulus frequency ratios and levels that are frequency-dependent and consistent with known mechanical properties of the cochlea.

Conclusions:

We propose a new DPOAE recording paradigm (variable-stimuli DP) using stimuli aligned to local cochlear properties which may improve early and accurate detection of decline in cochlear function.
Hardware Removal After Lisfranc Open Reduction and Internal Fixation Results in Improved Physical Function
Authors: Sroka Oliver , Campbell Megan , Thorne Tyler , Haller Justin , Rothberg David , Higgins Thomas , Marchand Lucas
Published: October 2024

OBJECTIVES:

The purpose of this study was to investigate whether hardware removal (HWR) after Lisfranc open reduction and internal fixation (ORIF) resulted in significant impact through PROMIS physical function (PF) and pain intensity (PI) scores.

METHODS:

Design:

Retrospective cohort.

Setting:

Level-1 trauma center.

Patient Selection Criteria:

Adult patients with isolated Lisfranc injuries who were treated through ORIF between 2002 and 2023 who had PROMIS PF and PI scores through 6 months follow-up were included. Patients were excluded if they received index treatment other than ORIF or underwent secondary surgical intervention before HWR. A subanalysis was performed at 1-year follow-up.

Outcome Measures and Comparisons:

Primary outcomes were PROMIS PF and PI scores. The Wilcoxon signed-rank test compared differences between PROMIS scores within the HWR group. The Wilcoxon ranked-sum test compared differences between HWR versus no HWR. Distributive MCID was calculated using the 0.5 SD method.

RESULTS:

There were 482 patients (489 feet) identified with isolated Lisfranc injuries. Seventy-seven feet underwent ORIF followed by HWR. Thirty feet underwent ORIF without HWR. The average age of the no HWR group was 45.8 (18.0–81.3) years versus the HWR group that was 38.7 (18.3–74.1) years (P = 0.053). Nineteen (63.3%) were women in the no HWR group compared with 33 (42.9%) in the HWR group (P = 0.084). HWR occurred an average of 4.43 months after ORIF. Patients who underwent HWR had a statistically significant increase in average PF scores (39.7–45.9, P < 0.001) at their standard 6 weeks (1.5 months) postoperative visit. HWR patients had a nonsignificant decrease in average PI scores (56.5–53.9, P = 0.24). Compared with those with retained hardware, the HWR group demonstrated a statistically significant net improvement in PF and PI scores from surgery, with an average improvement of 5.6 and 1.7, respectively (P = 0.002, 0.008).

CONCLUSIONS:

Patients experienced significant improvement in PROMIS PF scores for Lisfranc ORIF at 6 weeks after HWR. Compared with patients with retained hardware, they also experienced significant improvement in PROMIS PF and PI scores.

LEVEL OF EVIDENCE:

Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.
Subcutaneous Sweet Syndrome With Vasculitis Features: Case Report and Review
Authors: Tang Jia , Lv Bing
Published: October 2024

Background:

Subcutaneous Sweet Syndrome (SSS) is a rare variant of Sweet Syndrome characterized by neutrophilic infiltration of subcutaneous adipose tissue without vasculitis. The presence of vasculitis in SSS is uncommon and poses diagnostic challenges.

Case Presentation:

A 38-year-old female presented with a one-year history of recurrent painful erythematous nodules on her limbs and face. Physical examination revealed asymmetrical erythematous patches and tender subcutaneous nodules with central necrotic eschars on the lower limbs. Laboratory tests were unremarkable except for a mildly elevated erythrocyte sedimentation rate. Histopathological analysis showed significant neutrophilic infiltration within the adipose lobules and vascular walls, along with extravasation of red blood cells, indicating vasculitis. The patient responded promptly to systemic corticosteroids; however, symptoms recurred upon tapering, necessitating ongoing steroid therapy.

Discussion:

This case underscores the rare occurrence of vasculitis in SSS, expanding the histopathological spectrum of the disease. Literature review suggests that vasculitis in SSS may result from neutrophil-mediated vascular damage rather than immune complex deposition. The recurrent symptoms upon steroid tapering highlight the therapeutic challenges in managing SSS with vasculitis.

Conclusion:

Recognition of vasculitis in SSS is crucial for accurate diagnosis and effective management. Further research is warranted to elucidate the pathogenesis and develop targeted treatment strategies for SSS with vasculitis.
Rapidly Progressive Primary Cutaneous Gamma Delta T-Cell Lymphoma With FYN Gene Alteration
Authors: Azimpouran Mahzad , Bui Chau M. , Balzer Bonnie , Kitahara Sumire
Published: October 2024

Primary cutaneous gamma delta T-cell lymphoma (PCGDTCL) is a rare type of non-Hodgkin lymphoma accounting for <1% of primary cutaneous T-cell lymphomas. The exact cause of PCGDTCL is not known, however, it is thought that chronic antigen exposure in the skin may lead to immune dysregulation at the site, resulting in abnormal proliferation of mature, post-thymic cytotoxic gamma delta T cells. Mutations are the most common genetic alteration seen in PCGDTCL, while structural abnormalities such as gene fusions are not common. We report a case of PCGDTCL with atypical immunophenotypic features, including expression of CD5 with lack of cytotoxic marker expression, and a structural alteration leading to FYN deletion at exon 8. Recently, it was described that a deletion of the area between FYN exon 8 and TRAF3IP2 intron 2 results in a novel FYN::TRAF3IP2 fusion in peripheral T-cell lymphoma, not otherwise specified. We describe our patient's clinical course, differential diagnosis, and potential implications of FYN deletion on disease pathogenesis. To our knowledge, this is the first report of an FYN structural alteration to be described in PCGDTCL.