bluuebunny/crossref_metadata_2025 huggingface dataset:
Nuclear pore pathology underlying multisystem proteinopathy type 3‐related inclusion body myopathy
Authors: Izumi Rumiko , Ikeda Kensuke , Niihori Tetsuya , Suzuki Naoki , Shirota Matsuyuki , Funayama Ryo , Nakayama Keiko , Warita Hitoshi , Tateyama Maki , Aoki Yoko , Aoki Masashi
Published: December 2023

Objective

Multisystem proteinopathy type 3 (MSP3) is an inherited, pleiotropic degenerative disorder caused by a mutation in heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1), which can affect the muscle, bone, and/or nervous system. This study aimed to determine detailed histopathological features and transcriptomic profile of HNRNPA1‐mutated skeletal muscles to reveal the core pathomechanism of hereditary inclusion body myopathy (hIBM), a predominant phenotype of MSP3.

Methods

Histopathological analyses and RNA sequencing of HNRNPA1‐mutated skeletal muscles harboring a c.940G > A (p.D314N) mutation (NM_031157) were performed, and the results were compared with those of HNRNPA1‐unlinked hIBM and control muscle tissues.

Results

RNA sequencing revealed aberrant alternative splicing events that predominantly occurred in myofibril components and mitochondrial respiratory complex. Enrichment analyses identified the nuclear pore complex (NPC) and nucleocytoplasmic transport as suppressed pathways. These two pathways were linked by the hub genes NUP50, NUP98, NUP153, NUP205, and RanBP2. In immunohistochemistry, these nucleoporin proteins (NUPs) were mislocalized to the cytoplasm and aggregated mostly with TAR DNA‐binding protein 43 kDa and, to a lesser extent, with hnRNPA1. Based on ultrastructural observation, irregularly shaped myonuclei with deep invaginations were frequently observed in atrophic fibers, consistent with the disorganization of NPCs. Additionally, regarding the expression profiles of overall NUPs, reduced expression of NUP98, NUP153, and RanBP2 was shared with HNRNPA1‐unlinked hIBMs.

Interpretation

The shared subset of altered NUPs in amyotrophic lateral sclerosis (ALS), as demonstrated in prior research, HNRNPA1‐mutated, and HNRNPA1‐unlinked hIBM muscle tissues may provide evidence regarding the underlying common nuclear pore pathology of hIBM, ALS, and MSP.
Flame‐Retardant Polyurethane‐Based Solid‐State Polymer Electrolytes Enabled by Covalent Bonding for Lithium Metal Batteries
Authors: Wu Lin , Pei Fei , Cheng Dongming , Zhang Yi , Cheng Hang , Huang Kai , Yuan Lixia , Li Zhen , Xu Henghui , Huang Yunhui
Published: December 2023

Solid‐state lithium metal batteries (SSLMBs) have gained extensive attraction as one kind of next‐generation energy storage device. However, the drawbacks of flammability, low mechanical strength, and low ionic conductivity limit the further development of solid‐state polymer electrolytes (SPEs). In this work, a reactive flame‐retardant unit into the polymer framework via covalent bonding to create a nonflammable and stretchable polyurethane‐based SPEs is introduced. Meanwhile, the mechanical strength of the polymer backbone is increased by grafting a rigid benzene ring unit, which remarkably suppresses the lithium‐dendrite growth. As a result, these inflammable SPEs do not burn after contact with flames for 6 s. Furthermore, the obtained SPE expands the electrochemical stability window up to 5.1 V. Small monomers containing bromine decompose on the surface of lithium metal creating a LiBr riched solid electrolyte interface (SEI). Li|SPEs|Li symmetric battery offers a stable cycling life for more than 2100 h at 0.2 mA cm−2 and 0.2 mAh cm−2. The LiNi0.6Co0.2Mn0.2O2|SPEs|Li cell equipped with the integrated cathode delivers a 142.1 mAh g−1 capacity after 330 cycles at 0.3 C with 85.2% capacity retention.
Microfluidic Giant Polymer Vesicles Equipped with Biopores for High‐Throughput Screening of Bacteria
Authors: Heuberger Lukas , Messmer Daniel , dos Santos Elena C. , Scherrer Dominik , Lörtscher Emanuel , Schoenenberger Cora‐Ann , Palivan Cornelia G.
Published: December 2023

Understanding the mechanisms of antibiotic resistance is critical for the development of new therapeutics. Traditional methods for testing bacteria are often limited in their efficiency and reusability. Single bacterial cells can be studied at high throughput using double emulsions, although the lack of control over the oil shell permeability and limited access to the droplet interior present serious drawbacks. Here, a straightforward strategy for studying bacteria‐encapsulating double emulsion‐templated giant unilamellar vesicles (GUVs) is introduced. This microfluidic approach serves to simultaneously load bacteria inside synthetic GUVs and to permeabilize their membrane with the pore‐forming peptide melittin. This enables antibiotic delivery or the influx of fresh medium into the GUV lumen for highly parallel cultivation and antimicrobial efficacy testing. Polymer‐based GUVs proved to be efficient culture and analysis microvessels, as microfluidics allow easy selection and encapsulation of bacteria and rapid modification of culture conditions for antibiotic development. Further, a method for in situ profiling of biofilms within GUVs for high‐throughput screening is demonstrated. Conceivably, synthetic GUVs equipped with biopores can serve as a foundation for the high‐throughput screening of bacterial colony interactions during biofilm formation and for investigating the effect of antibiotics on biofilms.
Efficient and Stable Perovskite/Silicon Tandem Solar Cells Modulated with Triple‐Functional Passivator
Authors: Yang Tian , Mao Lin , Shi Jianhua , Zeng Peng , Li Faming , Gong Jue , Huang Xiyun , Wang Zhengshang , Cui Wen , Huang Di , Zhang Hao , Sun Yinqing , Fang Xiaoyu , Liu Zhengxin , Liu Mingzhen , Cui Xudong
Published: December 2023

Perovskite/silicon tandem solar cells (TSCs) have aroused much attentions in recent years. One of keys for achieving highly efficient and stable TSCs is to guarantee effective charge transfer, especially on the rough textured silicon substrate due to the poor adhesion between interlayers. Here, a 2‐fluoroisonicotinic acid (2‐FNA) additive that possesses fluorine (‐F), carboxylic acid (‐COOH), and pyridine nitrogen as functional groups in the perovskite precursor to assist the crystallization process is utilized. It shows that 2‐FNA can efficiently reduce the defects and suppress non‐radiative recombination of perovskite layers by bonding with the uncoordinated Pb2+ ions, formamidinium (FA+), and halide vacancies, leading to notably prolonged carrier lifetime. Most importantly, this found that 2‐FNA aids in the formation of better interfacial contact between the perovskite and C60 layer on top, thus enhancing the interfacial electron extraction therein, eventually leading to an increased power conversion efficiency (PCE) of 28.61% on champion perovskite/silicon TSCs from 27.08% on control counterparts. This work provides a practical route to further advance the PV performance and applicability of perovskite/silicon TSCs.
Synergy Unleashed: Piezo–Tribo Hybrid Harvester for Sustainable Power Generation Toward Augmented and Virtual Reality Applications
Authors: Prasanna Asokan Poorani Sathya , Anithkumar Monunith , Raaju Sundhar Arul Saravanan , Bincy Thanjan Shaji , Kim Sang‐Jae
Published: December 2023

Recently, piezo–tribo hybrid nanogenerators are developed using the synergistic effect. Exploration of multi‐crystalline piezoelectric materials adds the advantage of mechanically to electrically converting hybrid systems. On the way, the multi‐crystalline 0.3Ba0.7Ca0.3TiO3–0.7BaSn0.12Ti0.88O3 (BCST) materials are characterized by the structural, vibrational, and ferroelectric properties. The synergistic effect‐based polydimethylsiloxane/BCST hybrid composite film is prepared for multi‐energy harvesting. The triboelectric nanogenerator produces a maximum output voltage of 210 V. The hybrid device obtains the maximum output performance of 326 V. The harvested energy is used to charge commercial capacitors and power low‐power electronics. The signal processing and analysis unit is constructed for monitoring or functioning in real‐time finger movement. In the future, this kind of system can be coupled with augmented and virtual reality applications.
Synergism of sulfur availability and agronomic nitrogen use efficiency
Authors: Agyin‐Birikorang Sampson , Boubakry Cissé , Kadyampakeni Davie M. , Adu‐Gyamfi Raphael , Chambers Rachel A. , Tindjina Ignatius , Fuseni Abdul‐Rahman A.
Published: December 2023

Nutrient management strategies that exploit nutrient elements’ synergistic interaction to enhance nitrogen use efficiency (NUE) are needed for economic and environmental reasons. A field study was carried out during the 2020–2022 growing seasons at six locations in three countries: two each in the United States, Ghana, and Mali using three sulfur (S) sources with different bioavailability levels (micronized elemental S, untreated elemental S, and ammonium sulfate); applied at five S application rates: site‐specific recommended S rate (SR), 25%, 50%, 75%, and 125% of SR; and a single nitrogen (N) application rate (site‐specific recommended N rate) to comprehensively investigate the influence of S availability on NUE. Specific objectives were to evaluate the impact of S availability on corn (Zea mays L.) yield, N uptake, and NUE. Regardless of the S source and experimental site, the aboveground S and N uptake were strongly and positively correlated (r > 0.88). Increases in apparent N recovery efficiency and agronomic NUE occurred with corresponding increases in S application rate, irrespective of the site and S source. The combined data showed that the agronomic efficiency of applied N fertilizer sources could be enhanced significantly by increasing S availability in soils. With the rising N fertilizer costs in recent times, N losses from the applied fertilizer are a drain on farmers’ income and of environmental concern. Thus, increasing NUE is a needed strategy to safeguard against excessive N application, increase farm profits, and minimize N losses to the environment that could disrupt the ecosystem function.
Umbrella review and Delphi study on modifiable factors for dementia risk reduction
Authors: Rosenau Colin , Köhler Sebastian , Soons Lion M. , Anstey Kaarin J. , Brayne Carol , Brodaty Henry , Engedal Knut , Farina Francesca R. , Ganguli Mary , Livingston Gill , Lyketsos Constantine G. , Mangialasche Francesca , Middleton Laura E. , Rikkert Marcel G. M. Olde , Peters Ruth , Sachdev Perminder S. , Scarmeas Nikolaos , Salbæk Geir , van Boxtel Martin P. J. , Deckers Kay
Published: December 2023

A 2013 systematic review and Delphi consensus study identified 12 modifiable risk and protective factors for dementia, which were subsequently merged into the “LIfestyle for BRAin health” (LIBRA) score. We systematically evaluated whether LIBRA requires revision based on new evidence. To identify modifiable risk and protective factors suitable for dementia risk reduction, we combined an umbrella review of systematic reviews and meta‐analyses with a two‐round Delphi consensus study. The review of 608 unique primary studies and opinions of 18 experts prioritized six modifiable factors: hearing impairment, social contact, sleep, life course inequalities, atrial fibrillation, and psychological stress. Based on expert ranking, hearing impairment, social contact, and sleep were considered the most suitable candidates for inclusion in updated dementia risk scores. As such, the current study shows that dementia risk scores need systematic updates based on emerging evidence. Future studies will validate the updated LIBRA score in different cohorts.

Highlights

An umbrella review was combined with opinions of 18 dementia experts.

Various candidate targets for dementia risk reduction were identified.

Experts prioritized hearing impairment, social contact, and sleep.

Re‐assessment of dementia risk scores is encouraged.

Future work should evaluate the predictive validity of updated risk scores.
Lifetime occupational skill and later‐life cognitive function among older adults in the United States, Mexico, India, and South Africa
Authors: Kobayashi Lindsay C. , O'Shea Brendan Q. , Wixom Caroline , Jones Richard N. , Langa Kenneth M. , Weir David , Lee Jinkook , Wong Rebeca , Gross Alden L.
Published: December 2023

INTRODUCTION

We conducted a cross‐national comparison of the association between main lifetime occupational skills and later‐life cognitive function across four economically and socially distinct countries.

METHODS

Data were from population‐based studies of aging and their Harmonized Cognitive Assessment Protocols (HCAPs) in the US, South Africa, India, and Mexico (N = 10,037; Age range: 50 to 105 years; 2016 to 2020). Main lifetime occupational skill was classified according to the International Standard Classification of Occupations. Weighted, adjusted regression models estimated pooled and country‐specific associations between main lifetime occupational skill and later‐life general cognitive function in men and women.

RESULTS

We observed positive gradients between occupational skill and later‐life cognitive function for men and women in the US and Mexico, a positive gradient for women but not men in India, and no association for men or women in South Africa.

DISCUSSION

Main lifetime occupations may be a source of later‐life cognitive reserve, with cross‐national heterogeneity in this association.

Highlights

No studies have examined cross‐national differences in the association of occupational skill with cognition.

We used data from Harmonized Cognitive Assessment Protocols in the US, Mexico, India, and South Africa.

The association of occupational skill with cognitive function varies by country and gender.
Establishment and evaluation of an improved rat model of open abdomen
Authors: Liu Ye , Li Sicheng , Huang Jinjian , Li Ze , Chen Kang , Qu Guiwen , Wu Xiuwen , Ren Jianan
Published: December 2023

Introduction

This study aimed to establish an animal model of open abdomen (OA) through temporary abdominal closure via different techniques.

Methods

Adult male Sprague–Dawley rats were randomly divided into three groups: group A (OA with polypropylene mesh alone); group B (OA with polypropylene mesh combined with a patch); and group C (OA with polypropylene mesh and a sutured patch). Vital signs, pathophysiological changes, and survival rates were closely monitored in the rats for 7 days after surgery. Abdominal X‐rays and histopathological examinations were performed to assess abdominal organ changes and wound healing.

Results

The results showed no significant difference in mortality rates among the three groups (p > 0.05). However, rats in group B exhibited superior overall condition, cleaner wounds, and a higher rate of wound healing compared to the other groups (p < 0.05). Abdominal X‐rays indicated that varying degrees of distal intestinal obstruction in all groups. Histopathological examinations revealed fibrous hyperplasia, inflammatory cell infiltration, neovascularization, and collagen deposition in all groups. Group B demonstrated enhanced granulation tissue generation, neovascularization, and collagen deposition compared to the other groups (p < 0.05).

Conclusions

Polypropylene mesh combined with patches is the most suitable method for establishing an animal model of OA. This model successfully replicated the pathological and physiological changes in postoperative patients with OA, specifically the progress of abdominal skin wound healing. It provides a practical and reliable animal model for OA research.
Stringiness morphology for crosslinked polyacrylic pressure‐sensitive adhesives measured by peel testing with constant rate
Authors: Nakamura Yoshinobu , Yoshioka Daichi , Sato Tomonori , Takenaka Ayuna , Yoden Hiroyuki , Hikasa Shigeki , Urahama Yoshiaki , Hirai Tomoyasu , Fujii Syuji
Published: December 2023

To clarify the formation mechanism of front frame‐type morphology, the stringiness of crosslinked random copolymers of poly(n‐butyl acrylate‐acrylic acid) during a 180° peel test with a constant tensile rate was examined for various crosslinker contents and rates using a quartz adherend. Cohesive failure occurred for lower crosslinker content and rate, whereas interfacial failure with sawtooth‐type stringiness without a frame was observed for higher crosslinker content and rate. Front frame‐type stringiness was formed at the boundary of cohesive and interfacial failures. To clarify the formation mechanism, observation was conducted from the start of peel test until the equilibrium state. The sawtooth‐type stringiness with branches first formed at the tip. The adjoining branches were connected and the 2D frame was formed only on the adherend surface. The formed 2D frame developed toward the 3D walls and the front frame‐type was then completed. This is caused by the surface tension that acts to restrain the increase in the surface area. However, the surface area of the front frame‐type morphology was larger than the no frame‐type. The larger absorption of peeling stress by the formation of this morphology is expected to contribute to peel strength improvement.
Bio‐based waterborne polyurethane structural color films with high stability
Authors: He Yueqi , Zhu Yun , Xue Xiaojie , Song Yang , Hu Guyue , Wang Qirun , Jia Runping , Xu Xiaowei , Shi Jichao
Published: December 2023

In recent years, structural colors derived from photonic crystals (PCs) with a periodically ordered nanostructure are gorgeous and iridescent, but once their structure is destroyed, they will fade. In this work, the feasibility of the application of bio‐based waterborne polyurethanes (WPU) in structural color films was explored. The structural stability of PCs is enhanced bio‐based WPU as a kind of green product, which can replace solvent polyurethane one. A tung oil polyol (TOP) is fabricated by one‐step method with simple purification process and used to prepare waterborne polyurethane dispersions (WPUD). More introduction of TOP into the WPUD may help improve tensile strength and hydrophobic capability. It shows excellent mechanical properties with 16.8 MPa in tensile strength and water contact angle 109.5°. The SEM images confirmed that bio‐based WPU is more conducive to the self‐assembly of silica particles than traditional WPU.
Intercalated kaolinite with ammonium dihydrogen phosphate as an effective flame retardant to enhance the flame retardance and smoke suppression of epoxy resins
Authors: Yan Long , Wei Zheng , Guan Jingjing , Tang Xinyu , Liu Yan
Published: December 2023

To improve the compatibility and flame retardance of kaolinite (Kaol) in polymeric materials, ammonium dihydrogen phosphate (ADP) was intercalated into kaolinite to obtain a novel intercalated kaolinite (K‐ADP) for enhancing thermal stability, flame retardance, smoke suppression, and mechanical performance of epoxy resins (EPs). The results show that the presence of K‐ADP exerts a more positive effect on reducing the heat release and smoke generation of EPs than the same addition of Kaol. Condensed phase analysis shows that EP/K‐ADP composite generates more aromatic cross‐links in the condensed phase to reinforce the compactness and intumescence of char compared to EP/Kaol composite. Especially, 5 wt% K‐ADP confers a 43.7% reduction in peak heat release rate value and a 36.3% reduction in peak smoke production rate value to EP. Toxic gases analysis shows that K‐ADP conduces to inhibiting the release of combustible gases including isocyanates and aromatic volatiles, and generating incombustible gases including ammonia and carbon dioxide to reduce the intensity of EP combustion. The mechanical test shows that K‐ADP imparts less adverse impact on mechanical behavior to EP composites than Kaol due to the good dispersion and compatibility between K‐ADP with EP matrix.
Transfer of learning in histology: Insights from a longitudinal study
Authors: Darici Dogus , Flägel Kristina , Sternecker Katharina , Missler Markus
Published: December 2023

All anatomical educators hope that students apply past training to both similar and new tasks. This two‐group longitudinal study investigated the development of such transfer of learning in a histology course. After 0, 10, and 20 sessions of the 10‐week‐long course, medical students completed theoretical tasks, examined histological slides trained in the course (retention task), and unfamiliar histological slides (transfer task). The results showed that students in the histology group gradually outperformed the control group in all tasks, especially in the second half of the course,η2 = 0.268 (p < 0.001). The best predictor of final transfer performance was students’ retention performance after 10 sessions,β = 0.32 (p = 0.028), and theoretical knowledge after 20 sessions,β = 0.46 (p = 0.003). Results of eye tracking methodology further revealed that the histology group engaged in greater “visual activity” when solving transfer tasks, as indicated by an increase in the total fixation count,η2 = 0.103 (p = 0.014). This longitudinal study provides evidence that medical students can use what they learn in histology courses to solve unfamiliar problems but cautions that positive transfer effects develop relatively late in the course. Thus, course time and the complex relationship between theory, retention, and transfer holds critical implications for anatomical curricula seeking to foster the transfer of learning.
Sleep problems in children with autism spectrum disorder andattention‐deficit/hyperactivity disorder: A comparative study and effects on communication skills
Authors: Berenguer Carmen , Baixauli Inmaculada , Rosa Eva , De Stasio Simona
Published: December 2023

Sleep disturbances are highly prevalent among children with neurodevelopmental disorders, like Autism Spectrum Disorder (ASD) and Attention‐Deficit/Hiperactivity Disorder (ADHD). The first objective of this study is to examine the differences in sleep problems between a group of children with ASD without intellectual disabilities, a group with ADHD and a typically developing (TD) group. A second objective is aimed at analyzing the effects of sleep problems and symptom severity on their communication skills. Participants were 122 children between 7 and 12 years old distributed in three groups: 32 TD children, 47 children with ASD and 43 children with ADHD, matched on age and intelligence. Parents completed different questionnaires that measured sleep disturbances and communication skills. Findings show significant differences between the clinical groups and the TD group in most types of sleep disorders. Moreover, the group with ADHD showed significantly more sleep breathing disorders and hyperhidrosis in comparison with ASD and TD, as well as more total sleep problems. In contrast to ASD, the predictive power of sleep problems on communication difficulties was greater in the group with ADHD. The results of the mediation analysis indicate that in both groups, sleep problems partially mediate the relationship between symptoms and communication. This investigation highlights the need of considering sleep disorders when assessing communication skills in ASD and ADHD, given its indirect influence in this domain. Understanding the sleep dysfunctions of both conditions and their repercussions is crucial to develop adjusted interventions.
Evaluation of gadolinium‐based contrast agents in pregnant CD‐1 mice and subsequent in utero exposure of the developing offspring, including behavioral evaluations
Authors: Lewis Elise M. , Bussi Simona , Fretellier Nathalie , Clemens Guenther , Jones Paul , Tedoldi Fabio , Bourrinet Phillipe , Czupalla Oliver , Hirani Ella , Hoberman Alan M.
Published: December 2023

Introduction

The offspring of CD‐1 mice exposed during pregnancy to one of seven gadolinium‐based contrast agents (GBCAs) were evaluated for potential effects on postnatal development and behavior. The GBCAs, comprising four linear (gadopentetate dimeglumine, gadodiamide, gadobenate dimeglumine, and gadoxetate disodium) and three macrocyclic (gadoterate meglumine, gadoteridol, and gadobutrol), were administered via intravenous injection once daily from Gestation Day 6 through 17 following confirmed mating (Day 0) at doses of at least twice the human equivalent recommended clinical dose (i.e., 0.63 mmol Gd/kg for gadoxetate disodium and 2.5 mmol Gd/kg for the other GBCAs). All dams were allowed to deliver naturally. F0 generation females were monitored for maternal toxicity and gadolinium (Gd) levels in blood and brain. Offspring were evaluated for Gd levels in blood and brain at birth and on Day 70 postpartum. F1 generation mice were evaluated for survival and growth preweaning. Selected pups/litter were evaluated postweaning for sexual maturation, growth, and behavior. Gd was quantifiable in the brain of the F1 offspring on PND 1, with levels declining over time. There was no long‐term effect of any GBCA on the growth and development of any offspring. There was no impact on neurodevelopment, as assessed by brain histology and validated neurobehavioral tests, including a battery of functional observational tests, motor activity, and learning and memory as evaluated in the Morris water maze.

Conclusion

At the end of the postweaning period, the highest dose tested was considered the no‐observable‐adverse‐effect level (NOAEL) in the F0 and F1 offspring for all tested GBCAs.
Outcome of children with multicystic dysplastic kidney: Does involved side matter?
Authors: Yavuz Sevgi , Kıyak Aysel , Sander Serdar
Published: December 2023

Background

Multicystic dysplastic kidney (MCDK) is a common anomaly detected on antenatal ultrasound. We aimed to assess the profile of children with MCDK and to investigate whether the involved side has any effect on outcome.

Methods

Thirty‐nine patients with MCDK and 20 controls were enrolled. Patients who estimated glomerular filtration rate (eGFR) values over 90 mL/min/1.73 m2 were compared with controls. Comparison was made between the involved sides.

Results

MKDB was right‐sided in 20 (51.3%) and left‐sided in 19 (48.7%) patients. 33.3% had additional urinary tract abnormality, 10.2% had systemic abnormality. 82% showed contralateral kidney enlargement. 48.7% involuted, 17.9% underwent nephrectomy. 35.8% suffered from urinary tract infection (UTI). 5.1% had renal scarring (RS). 30% developed microalbuminuria. 12.8% complicated with hypertension. 17.9% progressed to chronic kidney disease (CKD). Hypertension was independent risk factor for developing CKD. Blood pressure, cystatin C and urine microalbumin/creatinine levels were increased, and eGFR values were decreased in patients compared to controls. No significant difference was found between the two sides for rates of involution, UTI, RS, nephrectomy, and additional abnormality. Cystatin C levels were higher on the right than left sides (p = .033).

Conclusion

Children with MCDK predispose to renal deterioration even at normal eGFR values. Although cystatin C levels tended to increase in right‐sided patients, the involved side seemed to have no significant effect on renal outcome. Hypertension was main determinant for progression to CKD in MCDK.
The development of an interdisciplinary theoretical framework for Forest School in the United Kingdom
Authors: Knight Sara , Coates Janine Kim , Lathlean Judith , Perez‐del‐Aguila Rossana
Published: December 2023

A growing evidence base has demonstrated the value of Forest School as an outdoor learning approach which supports a range of benefits including improved physical, social and mental wellbeing, increased confidence and self‐esteem and the development of problem‐solving skills. However, critics of Forest School have argued that a lack of theoretical coherence and detail risks the misinterpretation of Forest School and its pedagogy by both practitioners and researchers. This paper responds to these concerns, establishing a comprehensive and detailed theoretical framework for Forest School. Through a thorough examination of evidence supporting Forest School delivery, we examine the theoretical keystones of this pedagogical approach to inform an interdisciplinary theoretical understanding of Forest School. We argue that Forest School is a particular socially constructed approach to outdoor education, which is informed by social constructivist experiential learning theory. This is driven by two core components. First, play‐pedagogy, which includes the opportunity to experience risk and be creative. Next, biophilic interaction, which examines the human innate desire to be in nature. This is informed by the cultural origins of Forest School development as underpinned by Nordic notions of friluftsliv and by theories of place attachment. Taken together, this theoretical framework considers the breadth of knowledge that underpins Forest School and recognises its growing evidence base, which positions it as a rich and valuable pedagogical approach.
Simultaneous and trace‐level quantification of four benzene sulfonate potential genotoxic impurities in doxofylline active pharmaceutical ingredients and tablets using high‐performance liquid chromatography with ultraviolet detection
Authors: Xiao Tingyu , Lin Huaqing , Lao Jiekeng , Hu Xin , Chen Yucheng , Lei Yicong , Xu Mingzhi
Published: December 2023

In the production of doxofylline, the common occurrence of toxic p‐toluene sulfonate generation prompted the development and validation of a method using HPLC with ultraviolet detection (HPLC‐UV). This method is designed for detecting four potential genotoxic impurities (PGIs) present in both doxofylline drug substance and tablets, with a focus on the UV‐absorbing group p‐toluene sulfonate. The four impurities were methyl 4‐methylbenzenesulfonate (PGI‐1), ethyl 4‐methylbenzenesulfonate (PGI‐2), 2‐hydroxyethyl 4‐methylbenzenesulfonate (PGI‐3), and 2‐(4‐methylphenyl)sulfonyloxyethyl 4‐methylbenzenesulfonate (PGI‐4). In this method, chromatographic separation was achieved using a Waters Symmetry C18 column (250 mm × 4.6 mm, 5 μm). The mobile phases consisted of 20% acetonitrile as mobile phase A and pure acetonitrile as mobile phase B, operating in gradient elution mode at a flow rate of 1.0 mL/min. According to the guidelines of the International Conference on Harmonization, it was determined that this method could quantify four PGIs at 0.0225 μg/mL in samples containing 60 mg/mL. The validated approach demonstrated excellent linearity (R2 > 0.999) across the concentration range of 30%–200% (relative to 0.075 μg/mL doxofylline) for the four PGIs. The accuracy of this method for the four PGIs ranged from 94.8% to 100.4%. The reverse‐phase‐HPLC‐UV analytical method developed in this study is characterized by its speed and precision, making it suitable for the sensitive analysis of benzene sulfonate PGIs in doxofylline drug substances and tablets.
Development of antibody‐drug conjugates in cancer: Overview and prospects
Authors: Ruan Dan‐Yun , Wu Hao‐Xiang , Meng Qi , Xu Rui‐Hua
Published: December 2023

In recent years, remarkable breakthroughs have been reported on antibody‐drug conjugates (ADCs), with 15 ADCs successfully entering the market over the past decade. This substantial development has positioned ADCs as one of the fastest‐growing domains in the realm of anticancer drugs, demonstrating their efficacy in treating a wide array of malignancies. Nonetheless, there is still an unmet clinical need for wider application, better efficacy, and fewer side effects of ADCs. An ADC generally comprises an antibody, a linker and a payload, and the combination has profound effects on drug structure, pharmacokinetic profile and efficacy. Hence, optimization of the key components provides an opportunity to develop ADCs with higher potency and fewer side effects. In this review, we comprehensively reviewed the current development and the prospects of ADC, provided an analysis of marketed ADCs and the ongoing pipelines globally as well as in China, highlighted several ADC platforms and technologies specific to different pharmaceutical enterprises and biotech companies, and also discussed the new related technologies, possibility of next‐generation ADCs and the directions of clinical research.
Biochemical progression free and overall survival among Black men with stage IV prostate cancer in South Africa: Results from a prospective cohort study
Authors: Pumpalova Yoanna S. , Ramakrishnan Adarsh , May Michael , Pentz Audrey , Minkowitz Shauli , Doherty Sean , Singh Elvira , Chen Wenlong Carl , Rebbeck Timothy R. , Neugut Alfred I. , Joffe Maureen
Published: December 2023

Background

Men of African descent are disproportionately affected by prostate cancer (PCa), and many have metastatic disease at presentation. In South Africa (SA), androgen deprivation therapy (ADT) is the first‐line treatment for stage IV PCa.

Objective

To identify predictors of overall survival (OS) in Black South African men with stage IV PCa treated with ADT.

Design, Setting, and Participants

Men diagnosed with prostate cancer (3/22/2016–10/30/2020) at Chris Hani Baragwanath Academic Hospital in Soweto, Johannesburg, were recruited for the Men of African Descent with Cancer of the Prostate study. We included men with newly diagnosed stage IV PCa treated with ADT who had a prostate‐specific antigen (PSA) level drawn prior to initiation of ADT and had ≥1 PSA drawn ≥12 weeks after ADT start.

Outcomes Measures and Statistical Analysis

We used Kaplan–Meier statistics to estimate OS and Cox regression models to identify predictors of OS.

Results and Limitations

Of the 1097 men diagnosed with prostate cancer, we included 153 men with stage IV PCa who received ADT and met PSA requirements. The median age was 68.0 years (interquartile range 64–73 years). Median OS from time of ADT initiation was 3.39 years (95% confidence interval (CI): 3.14%–noncalculable), while biochemical progression‐free survival was 2.36 years (95% CI: 2.03%–3.73%). Biochemical progression (HR 3.52, 95% CI: 1.85%–6.70%), PSA nadir level >4 ng/mL (HR 3.77, 95% CI: 1.86%–7.62%), alkaline phosphatase level at diagnosis >150 IU/dL (HR 3.09, 95% CI: 1.64%–5.83%), and hemoglobin at diagnosis <13.5 g/dL (HR 2.90, 95% CI: 1.28%–6.56%) were associated with worse OS.

Conclusions

In this study, we identified factors associated with poor OS among Black South African men with stage IV PCa treated with ADT. These factors may be useful in identifying patients for upfront treatment escalation, including the use of docetaxel chemotherapy or escalation of therapy at the time of biochemical progression.

Patient Summary

In this study, we found that high alkaline phosphatase level, anemia at diagnosis, and high PSA nadir after initiation of androgen deprivation therapy are associated with worse overall survival among Black South African men treated with androgen deprivation therapy for metastatic prostate cancer.
Coherent Evaluation of Energy Efficiency for Microwave Catalytic Reactors Based on Reaction Equilibrium
Authors: Suguro Takuya , Kishimoto Fuminao , Movick William J. , Takanabe Kazuhiro
Published: December 2023

Microwave‐driven catalytic processes have attracted the attention of many researchers and industries as these processes are powerful strategies for use in industrial electrification. However, undetectable hot spots inside the catalyst bed can be misleading in terms of the deceptive effects of microwaves on acceleration of catalytic reactions because of the lack of physicochemical knowledge about these processes. In this paper, the hot spots temperatures were estimated based on catalytic ammonia (NH3) synthesis/decomposition equilibrium. The reaction temperature estimated from the chemical equilibrium was more than 100 °C higher than the catalyst bed surface temperature measured with an infrared thermometer under microwave irradiation. Assuming a formation of very steep local high temperature fields, rigorous kinetic analysis led to an estimate that the active site fraction which reaches the high temperature was only about 10 % of total sites. Compared with a resistivity heating furnace, the energy input was reduced by more than 85 % under microwave irradiation. The temperature estimated by the chemical equilibrium was almost corresponding to the temperature estimated by an oscillation of extended X‐ray absorption fine structure recorded under microwave irradiation. This paper presents a proposal for a method to estimate hot spots based on thermodynamic equilibrium, yielding a quantitative evaluation of energy consumption reduction caused by microwaves.
The Need for Dynamic Process Simulation: A Review of Offshore Power‐to‐X Systems
Authors: Rentschler Philipp , Klahn Christoph , Dittmeyer Roland
Published: December 2023

The integration of offshore wind energy into Power‐to‐X (PtX) process chains offers opportunities for the efficient use of renewable energy. This article analyzes different PtX process chain configurations and their adaptation to the offshore environment. However, direct coupling of PtX platforms with fluctuating electrical energy poses major challenges. Dynamic process simulation is presented for analysis of different plant configurations and operating strategies. The article emphasizes the need for interdisciplinary research to consider technological as well as economic and environmental aspects.
L'efficacité des annonces publicitaires persuasives incitant à la distanciation sociale
Authors: BelhadjYoussef Mohamed Hatem , Besbes Sahli Alia
Published: December 2023

This research aims to test the impact of persuasive ads encouraging social distancing in the face of the coronavirus. A survey of 208 individuals found that the effectiveness of this communication depends mainly on the attitude toward the advertisement and the perceived effectiveness of the recommendation. However, while the negative impact of consumers' dispositional skepticism on their attitude toward the advertisement has been confirmed, the impact of trust in the advertiser, as well as the moderating effects of situational skepticism and altruism have not been established.
A Psychoanalysis of Player Unknown's Battlegrounds (PUBG) in the Context of India 2020–2021
Authors: Debnath Achintya
Published: December 2023

This article is based on field surveys and interviews among mobile users. It provides a heuristic framework for understanding the dynamics of violent content, recent issues regarding banning PUBG (player unknown's battlegrounds) video games, and the complex characteristics of its perspectives. More precisely, it brings up an explanation and relation between violence and certain video games primarily focused on mobile user gamers who play PUBG (or Free Fire or both). Furthermore, this study throws light on the hot debate of banning PUBG in India in 2020–21 and the context of oversimplified assumptions behind its ban. The entire frame of this article is based on individual interviews of mobile users and their thoughts and experiences on the matter. For this purpose, fifty interviews have been conducted among gamers–players who play PUBG, Free Fire, or both. Furthermore, this research will contribute to the video game debate that has been going on regarding the relation between violence and games which started as early as the 1970s (Kowert and Quandt 2021).
Liz Przybylski. 2020. Hybrid Ethnography: Online, Offline, and In Between. SAGE Publications, Inc.
Authors: Ackfeldt Anders
Published: December 2023

As social media proliferates globally, affecting over half the world's population, ethnographic research must adapt to evolving modes of communication and representation. Liz Przybylski's book Hybrid Ethnography: Online, Offline, and In Between offers an accessible, practical guide to hybrid ethnography spanning both digital and physical spaces. Covering project formulation, research ethics, site selection, data collection, analysis, and writing, the book draws on the author's experience studying hip‐hop culture across the United States and Canada. Key strengths highlighted include the continuous focus on ethical considerations and the book's utility for researchers at all stages. The modular chapter design also allows for targeted consultation by researchers. Overall, this timely volume serves as an essential, durable guide for ethnographers navigating an increasingly digitized social landscape where subjects have greater control over self‐representation. It receives an enthusiastic recommendation for students and scholars alike.
Limits to species distributions on tropical mountains shift from high temperature to competition as elevation increases
Authors: Chen Jinlin , Lewis Owen T.
Published: December 2023

Species turnover with elevation is a widespread phenomenon and provides valuable information on why and how ecological communities might reorganize as the climate warms. It is commonly assumed that species interactions are more likely to set warm range limits, while physiological tolerances determine cold range limits. However, most studies are from temperate systems and rely on correlations between thermal physiological traits and range limits; little is known about how physiological traits and biotic interactions change simultaneously along continuous thermal gradients. We used a combination of correlational and experimental approaches to investigate communities of Drosophila flies in rainforests of the Australian Wet Tropics, where there is substantial species turnover with elevation. Our experiments quantified individual‐level and population‐level responses to temperature, as well as the impact of interspecific competition under different temperature regimes. Species' distributions were better explained by their performance at extreme temperatures than by their thermal optima. Upper thermal limits varied less among species than lower thermal limits. Nonetheless, these small differences were associated with differences in the centered elevation of distribution. Low‐elevation species were not those with the lowest tolerance to cold, suggesting that cold temperatures were not limiting their abundance at high elevations. Instead, under upland temperature regimes, abundances of these low‐elevation species were reduced by competition with a high‐elevation species, in both short‐ and long‐term competition experiments. Our results demonstrate that high‐elevation species are confined to their current ranges by high temperatures at lower elevations, indicating that their ranges will be highly sensitive to future warming. Counter to expectation, species interactions strongly influenced community composition at cooler, high‐elevation sites. Together, these results raise the possibility that tropical communities differ from better‐studied temperate communities in terms of the relative importance of biotic interactions and abiotic factors in shaping community composition and how the impact of these factors will change as temperatures increase.
Invasive haemodynamics at rest and exercise in cardiac amyloidosis
Authors: Holt Margrethe Flesvig , Flø August , Ravnestad Håvard , Bjørnø Vilde , Gullestad Lars , Andreassen Arne K. , Broch Kaspar , Gude Einar
Published: December 2023

Aims

Our aim was to investigate haemodynamics at rest and during exercise in patients with transthyretin cardiomyopathy (ATTR‐CM) in light of the 2022 European Society of Cardiology (ESC) and European Respiratory Society (ERS) guidelines on pulmonary hypertension (PH).

Methods and results

We performed right heart catheterization (RHC) in 57 subjects with ATTR‐CM. The proportion of patients with PH was 77% according to the 2022 guidelines versus 47% when applying the 2015 guidelines. Isolated post‐capillary PH and combined pre‐ and post‐capillary PH were most prevalent. Thirty‐six patients underwent a supine bicycle cardiopulmonary exercise test during RHC. Exercise‐induced PH was defined as an increase in mean pulmonary arterial pressure from rest to exercise per increase in cardiac output (ΔmPAP/ΔCO) of > 3 mmHg/L/min. An increase in pulmonary arterial wedge pressure per change in cardiac output (ΔPAWP/ΔCO) from rest to exercise >2 mmHg/L/min was considered suggestive of post‐capillary exercise‐induced PH. All but two patients who exercised during RHC developed exercise‐induced PH. The median ΔmPAP/ΔCO was 7.2 mmHg/L/min and ΔPAWP/ΔCO was 5.1 mmHg/L/min. The median ΔRAP/ΔCO was 3.6 mmHg/L/min and ΔRAP/ΔPAWP was 0.6 mmHg/L/min.

Conclusions

Most patients with ATTR‐CM have isolated post‐capillary or combined pre‐ and post‐capillary PH at rest, and almost all patients develop exercise‐induced PH with a large post‐capillary component. There was a pronounced, but balanced increase in atrial pressures on exercise.
Role of vericiguat in management of patients with heart failure with reduced ejection fraction after worsening episode
Authors: Olivella Aleix , Almenar‐Bonet Luis , Moliner Pedro , Coloma Emmanuel , Martínez‐Rubio Antoni , Paz Bermejo Marco , Boixeda Ramon , Cediel German , Méndez Fernández Ana Belén , Facila Rubio Lorenzo
Published: December 2023

Worsening heart failure (HF) is a vulnerable period in which the patient has a markedly high risk of death or HF hospitalization (up to 10% and 30%, respectively, within the first weeks after episode). The prognosis of HF patients can be improved through a comprehensive approach that considers the different neurohormonal systems, with the early introduction and optimization of the quadruple therapy with sacubitril–valsartan, beta‐blockers, mineralocorticoid receptor antagonists, and inhibitors. Despite that, there is a residual risk that is not targeted with these therapies. Currently, it is recognized that the cyclic guanosine monophosphate deficiency has a negative direct impact on the pathogenesis of HF, and vericiguat, an oral stimulator of soluble guanylate cyclase, can restore this pathway. The effect of vericiguat has been explored in the VICTORIA study, the largest chronic HF clinical trial that has mainly focused on patients with recent worsening HF, evidencing a significant 10% risk reduction of the primary composite endpoint of cardiovascular death or HF hospitalization (number needed to treat 24), after adding vericiguat to standard therapy. This benefit was independent of background HF therapy. Therefore, optimization of treatment should be performed as earlier as possible, particularly within vulnerable periods, considering also the use of vericiguat.
Changes over time in patient‐reported outcomes in patients with heart failure
Authors: Jaarsma Tiny , Kato Naoko P. , Klompstra Leonie , Ben Gal Tuvia , Boyne Josiane , Hägglund Eva , Vellone Ercole , Hagenow Andreas , Evangelista Lorraine S. , Mårtensson Jan , Strömberg Anna
Published: December 2023

Aim

This paper describes the trajectory during 1 year of four patient‐reported outcomes (PROs), namely, sleep, depressive symptoms, health‐related quality of life (HrQoL), and well‐being, in patients with heart failure (HF), their relationship and the patient characteristics associated with changes in these PROs.

Methods and results

Data analyses of PROs from 603 patients (mean age 67 years; 29% female, 60% NYHA II) enrolled in the HF‐Wii study. On short term, between baseline and 3 months, 16% of the patients experienced continuing poor sleep, 11% had sustained depressive symptoms, 13% had consistent poor HrQoL, and 13% consistent poor well‐being. Across the entire 1‐year period only 21% of the patients had good PRO scores at all timepoints (baseline, 3, 6, and 12 months). All others had at least one low score in any of the PROs at some timepoint during the study. Over the 12 months, 17% had consistently poor sleep, 17% had sustained symptoms of depression, 15% consistently rated a poor HrQoL, and 13% poor well‐being. Different patient characteristics per PRO were associated with a poor outcomes across the 12 months. Age, education, New York Heart Association, and length of disease were related to two PRO domains and submaximal exercise capacity (6 min test), co‐morbidity, and poor physical activity to one.

Conclusion

In total, 79% of the patients with HF encountered problems related to sleep, depressive symptoms, HrQoL, and well‐being at least once during a 1‐year period. This underscores the need for continuous monitoring and follow‐up of patients with HF and the need for dynamic adjustments in treatment and care regularly throughout the HF trajectory.