bluuebunny/crossref_metadata_2025 huggingface dataset:
The versatility of the scapular free flap: A workhorse flap? A systematic review and meta‐analysis
Authors: Escobar‐Domingo Maria J. , Bustos Valeria P. , Akintayo Rachel , Mahmoud Amir‐Ala , Fanning James E. , Foppiani Jose A. , Miller Amitai S. , Cauley Ryan P. , Lin Samuel J. , Lee Bernard T.
Published: June 2024

Background

The scapular free flap (SFF) is essential in complex reconstructive surgery and often indicated in complex defects with compromised or poor local tissue integrity. This review aims to assess the versatility and reliability of the SFF during reconstruction.

Methods

A comprehensive literature review of multiple databases was conducted following the PRISMA guidelines. An analysis of pooled data was performed to evaluate flap failure rate for any anatomical unit using SFF as the primary endpoints. Secondary endpoints included other complication rates after reconstruction such as partial flap loss, revision surgery, fistula, hematoma, and infection.

Results

A total of 110 articles were included, with 1447 pooled flaps. The main recipient site was the head and neck region (89.0%). Major indications for reconstruction were malignancy (55.3%), burns (19.2%), and trauma (9.3%). The most common types of flaps were osteocutaneous (23.3%), cutaneous (22.6%), and chimeric (18.0%). The pooled flap failure rate was 2% (95%CI: 1%–4%). No significant heterogeneity was present across studies (Q statistic 20.2, p = .69; I2 .00%, p = .685). Nonscapular supplementary flaps and grafts were required in 61 cases. The average length and surface area of bone flaps were 7.2 cm and 24.8cm2, respectively. The average skin paddle area was 134.2cm2.

Conclusion

The SFF is a useful adjunct in the reconstructive surgeon's armamentarium as evidence by its intrinsic versatility and diverse clinical indications. Our data suggest a low failure rate in multicomponent defect reconstruction, especially in head and neck surgery. SFFs enable incorporation of multiple tissue types and customizable dimensions—both for vascularized bone and cutaneous skin—augmenting its value in the microsurgeon's repertoire as a chimeric flap. Further research is necessary to overcome the conventional barriers to SFF utilization and to better comprehend the specific scenarios in which the SFF can serve as the preferred alternative workhorse flap.
Fast 3D fMRI acquisition with high spatial resolutions over a reduced FOV
Authors: Luo Qingfei , Sun Kaibao , Dan Guangyu , Zhou Xiaohong Joe
Published: June 2024

Purpose

To develop and demonstrate a fast 3D fMRI acquisition technique with high spatial resolution over a reduced FOV, named k‐t 3D reduced FOV imaging (3D‐rFOVI).

Methods

Based on 3D gradient‐echo EPI, k‐t 3D‐rFOVI used a 2D RF pulse to reduce the FOV in the in‐plane phase‐encoding direction, boosting spatial resolution without increasing echo train length. For image acceleration, full sampling was applied in the central k‐space region along the through‐slab direction (kz) for all time frames, while randomized undersampling was used in outer kz regions at different time frames. Images were acquired at 3T and reconstructed using a method based on partial separability. fMRI detection sensitivity of k‐t 3D‐rFOVI was quantitively analyzed with simulation data. Human visual fMRI experiments were performed to evaluate k‐t 3D‐rFOVI and compare it with a commercial multiband EPI sequence.

Results

The simulation data showed that k‐t 3D‐rFOVI can detect 100% of fMRI activations with an acceleration factor (R) of 2 and ˜80% with R = 6. In the human fMRI data acquired with 1.5‐mm spatial resolution and 800‐ms volume TR (TRvol), k‐t 3D‐rFOVI with R = 4 detected 46% more activated voxels in the visual cortex than the multiband EPI. Additional fMRI experiments showed that k‐t 3D‐rFOVI can achieve TRvol of 480 ms with R = 6, while reliably detecting visual activation.

Conclusions

k‐t 3D‐rFOVI can simultaneously achieve a high spatial resolution (1.5‐mm isotropically) and short TRvol (480‐ms) at 3T. It offers a robust acquisition technique for fast fMRI studies over a focused brain volume.
Tongue pressure is a strong predictor of recommendation for gastrostomy in amyotrophic lateral sclerosis
Authors: Mendes Amanda E. , Silva Guilherme D. , Jorge Frederico M. H. , Callegaro Dagoberto
Published: June 2024

Introduction/Aims

Objective and practical biomarkers to determine the need for gastrostomy in patients with amyotrophic lateral sclerosis (ALS) are lacking. Tongue pressure (TP) is a promising biomarker because it is associated with bulbar dysfunction. The aims of this study were to evaluate the association of TP with the need for gastrostomy, and to determine its optimal cut‐off value.

Methods

This prospective observational study included participants with ALS taking nutrition orally. TP was evaluated using the Iowa Oral Performance Instrument. Need for gastrostomy as determined by a multidisciplinary team during a 12‐month follow up period was recorded. Associations between TP and need for gastrostomy placement were performed. ROC curve analysis determined the optimal cut‐off value of TP to predict gastrostomy.

Results

Of 208 screened participants, 119 were included. Gastrostomy was indicated in 45% (53), in a 12‐month follow up period. TP of ≤20 kPA was a strong predictor of gastrostomy indication (OR 11.8, CI 95% [4.61, 34.7], p < .001). The association persisted even after adjustment for weight loss, pneumonia, prolonged feeding duration, Revised ALS Functional Rating Scale score, and American Speech‐Language‐Hearing Association scale score (OR 4.51, CI 95% [1.50, 14.9], p = .009). By receiver operating characteristic curve analysis, 20 kPA represented the optimal cut‐off value (sensitivity 0.75, specificity 0.89).

Discussion

TP is a strong independent predictor of gastrostomy indication in the subsequent 12 months in patients with ALS, with good sensitivity and specificity at a cutoff value of ≤20 kPA, suggesting that it may be a promising biomarker in clinical practice.
Retention of p-Chip microtransponders and posttagging survival of small-bodied stream fishes
Authors: Spooner Joseph , Spurgeon Jonathan
Published: June 2024

Objective

Obtaining demographic rates often requires complex open-population capture–mark–recapture (CMR) study designs. Conducting such studies for small-bodied fishes has been limited in part by excessive mortality after tagging procedures and poor tag retention. As new tag types emerge, information regarding fish survival and tag retention over varying time scales may benefit resource managers to effectively plan future CMR studies. The p-Chip microtransponder is a 500- × 500- × 100-μm tag that is inserted subcutaneously and is read with a handheld laser. Each tag contains a nine-digit unique identification number. P-Chip microtransponder tags have been used on a limited number of small-bodied fishes, with relatively high rates observed for fish survival and tag retention. Information on posttagging survival and retention of p-Chip microtransponder tags across a range of small-bodied fish species and tagging locations is needed to inform their effectiveness in future CMR studies.

Methods

We quantified survival and tag retention after p-Chip microtransponder implantation in Creek Chub Semotilus atromaculatus and Northern Pearl Dace Margariscus nachtriebi in a laboratory environment, and retention of p-Chip microtransponder tags in Northern Pearl Dace was also quantified over a year-long field study. We marked 56 Creek Chub and 9 Northern Pearl Dace in the laboratory with p-Chip microtransponder tags and compared them to an equal number of unmarked individuals over 90 days. We marked 1990 Northern Pearl Dace and conducted recapture events through four seasons (June, September, and October 2022 and June 2023) in four headwater streams of Nebraska.

Result

Survival for Creek Chub was 85% (standard error [SE] = 5.9) and did not differ from control fish survival (95%; SE = 3.2) in the 90-day laboratory experiment. Survival for Northern Pearl Dace was 89% (SE = 11.0) and did not differ from that of control fish (100%) in the laboratory experiment. Tag retention was 89% (SE = 4.6) for Creek Chub and 100% for Northern Pearl Dace in the laboratory. The p-Chip microtransponder performed well during the CMR field study, with tag retention for Northern Pearl Dace at 94% across 374 days.

Conclusion

Our results suggest that the p-Chip microtransponder minimally affected small-bodied fish survival and had high tag retention in both the laboratory and field studies. Thus, the p-Chip microtransponder tag may be appropriate for use in small-bodied fishes when individual identification is needed in a CMR study.
Enhancing nutritional formula expiry monitoring: A quality improvement project in a tertiary‐level hospital in Riyadh, Saudi Arabia
Authors: Albalawi Sawsan , AlObari Rania , AlMidani Eyad , Malkawi Rafat , Abosaleh Dima , Qarni Sozan , Subrayan Sasikalan , Almuteiry Saif , Abel‐Reyes Leodevina , Alhazaa Bader , Alhuthil Raghad
Published: June 2024

Background

Nutrition is a vital part of any treatment plan. This may include providing nutritional formulas during hospitalization and afterward. However, reported incidents showed that we had issues with nutritional formula expiry monitoring at our hospital with low compliance to Joint Commission International Standards (MMU.3.1): “There is a process for storage of medications and nutritional products that require special consideration.” Therefore, a “Nutritional Formula Expiry Monitoring” project was created to decrease hospital safety incidents related to expired nutritional formulas from an average of 28 in 2015 to zero by 2018.

Materials and Methods

A quality improvement model was developed to map the existing formula processes. Several proposed ideas were tested including performing a hospital‐wide audit to examine possible risks and practices, developing a hospital policy, flow charts, forms, and audit tools, and providing educational presentations.

Results

A total of 40 units in the hospital were included in the implementation. After implementing all the change ideas, the system for monitoring the expiry of the nutritional formula was standardized, and the number of reported incidents related to the nutritional formula decreased from 28 in the third quarter of 2015 to one in the first quarter of 2018.

Conclusion

This project provided step‐by‐step instructions for improving storing, delivering, and monitoring of nutritional formula. Consequently, the incidences of expired formula and cost wasting were successfully decreased, which increased safe administration and prevented patients from receiving expired nutritional formula. This project can be implemented in various healthcare settings.
Instead of with a rowboat, search for the north star by navigating a sailboat through turbulent times
Authors: Hoedemakers Juri , de Bruin Cardoso Isabel , van Overbeeke Philine , Meijs Lucas
Published: June 2024

We respond to von Schnurbein and Ahmad's (2019) metaphor of rowing to elucidate the inflexibility of foundations. We suggest that perhaps a sailboat would be more appropriate to finding the north star and add a fifth proposition: a participatory decision‐making process that includes balanced feedback. This approach, though not new, can pose risks such as misaligned priorities and ineffective decisions. To navigate these challenges, the introduction of a "court jester" role is proposed, encouraging open dialogue and critical self‐reflection. The flexibility akin to sailing, where adjustments are made based on feedback, is advocated for effective and dynamic foundation governance.
Auxiliary model maximum likelihood gradient‐based iterative identification for feedback nonlinear systems
Authors: Liu Lijuan , Li Fu , Ma Junxia , Xia Huafeng
Published: June 2024

This article considers the iterative identification problems for a class of feedback nonlinear systems with moving average noise. The model contains both the dynamic linear module and the static nonlinear module, which brings challenges to the identification. By utilizing the key term separation technique, the unknown parameters from both linear and nonlinear modules are included in a parameter vector. Furthermore, an auxiliary model maximum likelihood gradient‐based iterative algorithm is derived to estimate the unknown parameters. In addition, an auxiliary model maximum likelihood stochastic gradient algorithm is derived as a comparison. The numerical simulation results indicate that the auxiliary model maximum likelihood gradient‐based iterative algorithm can effectively estimate the parameters of the feedback nonlinear systems and get more accurate parameter estimates than the auxiliary model maximum likelihood stochastic gradient algorithm.
Osteogenic and angiogenic dual small molecule loaded chitosan nanoparticles for vascularized bone regeneration
Authors: Büyük Nisa İrem , Torun Köse Gamze
Published: June 2024

In recent years, the preference for small molecules has increasingly overshadowed growth factors. In this study, an osteogenic factor, DIPQUO, and an angiogenic factor, a VEGF inducer, GS4012, were encapsulated in chitosan nanoparticles (NPs) to provide vascularized bone regeneration. The encapsulation efficiencies of DIPQUO and GS4012 were 79% and 75%, respectively. The release profiles were 69% and 41% within the first 3 h, followed by 13 days to complete the release of all materials. The synthesis of NPs was validated via FT‐IR analysis, while their thermal properties were assessed via Differential scanning calorimetry (DSC). For in vitro osteogenesis, mesenchymal stem cells isolated from rat bone marrow were investigated by MTS, ALP, and various histological stains (H&E, alizarin red, and von Kossa). In the context of angiogenesis, endothelial cells derived from the peripheral blood of rats were isolated, characterized, and their capabilities to migrate and form vessels assessed. This study demonstrated that two different small molecules act synergistically to enable bone differentiation and may contribute to vascularized bone regeneration.
A fully bio‐based epoxy resin with excellent mechanical properties combines flame retardancy and degradability
Authors: Chen Yuquan , Ren Bin , Li Xuemei , Rao Suhan , Guo Zhangyi , Li Yufei , Huang Ying , Kang Ming , Li Xiuyun
Published: June 2024

Traditional epoxy resins are made from non‐renewable fossil resources, which are difficult to reprocess and recycle, and their flammability makes them unsafe during use. In this experiment, an epoxy resin containing Schiff base (TA‐VAN‐EP) was synthesized successfully with biomass‐derived raw materials. This new material not only had favorable mechanical properties but also had good flame retardancy and degradation properties. The chemical structure of TA‐VAN‐EP was characterized by Fourier transform infrared (FTIR) spectroscopy and 1H nuclear magnetic resonance (NMR) spectroscopy. Its mechanical properties, thermal stability, flame‐retardant properties, and other properties were tested. The results showed that, compared with the pure epoxy resin (EP), the mechanical properties of TA‐VAN‐EP were significantly improved, and the glass transition temperature (Tg) was increased from 152°C to 190°C. Additionally, TA‐VAN‐EP reached a V‐1 rating during the UL‐94 test, and the limited oxygen index (LOI) value increased from 24.7% to 28.4%. Also, the total heat release (THR), smoke production rate (SPR), and total smoke release (TSR) decreased extremely. Moreover, TA‐VAN‐EP demonstrated good degradation performance under acidic conditions. In conclusion, this work provided a new idea for the production of bio‐based flame‐retardant epoxy resin with promising degradable abilities and mechanical properties.
Mechanical and thermal properties of fumed silica‐incorporated silane‐terminated urethane/epoxy‐interpenetrating polymer network nanocomposites
Authors: Akın Emre , Çakır Mustafa , Kartal İlyas
Published: June 2024

In this study, it was aimed to improve the mechanical and thermal properties of epoxy materials based on diglycidyl ether of bisphenol‐A‐based. For this purpose, three different nanocomposite materials were prepared at various ratios including a fumed silica nanoparticle‐reinforced epoxy nanocomposite (FSN), an epoxy/silane‐terminated urethane (STU) hybrid interpenetrating polymer network (IPN) nanocomposite (SHIN), and a fumed silica‐reinforced epoxy/STU hybrid IPN nanocomposite (FSHIN). While synthesizing SHIN, 3‐isocyanato propyl trimethoxy silane (ICPTMS) and poly (hexamethylene carbonate) diol were used. The synthesized STU polymer chains were crosslinked by reacting them with TEOS via the sol–gel process. Therefore, hybrid networks were obtained. Moreover, fumed silica nanoparticles were incorporated into the hybrid networks via the sol–gel process for FSHINs. The three different nanocomposite materials exhibited much more improved properties than the neat epoxy. The most prominent nanocomposite was FSHIN. In comparison with the neat epoxy, Young's modulus, ultimate tensile strength, and Izod impact resistance values increased at ratios of 53%, 50%, and 223%, respectively. Glass transition temperature values and char yield values increased substantially in all nanocomposites. However, thermal decomposition temperatures increased only for FSNs. Moreover, these values for FSHINs that were very close to those of the neat epoxy were considerably higher than those of SHINs.

Highlights

Fumed silica‐incorporated silane‐terminated urethane/epoxy IPN nanocomposites.

Substantially improved mechanical properties and impact resistance.

Improved thermal stability.
Genome wide association studies on seven yield‐related traits of 183 rice varieties in Bangladesh
Authors: Roy Nilanjan , Kabir Acramul Haque , Zahan Nourin , Mouna Shahba Tasmiya , Chakravarty Sakshar , Rahman Atif Hasan , Bayzid Md. Shamsuzzoha
Published: June 2024

Rice genetic diversity is regulated by multiple genes and is largely dependent on various environmental factors. Uncovering the genetic variations associated with the diversity in rice populations is the key to breed stable and high yielding rice varieties. We performed genome wide association studies (GWASs) on seven rice yielding traits (grain length, grain width, grain weight, panicle length, leaf length, leaf width, and leaf angle) based on a population of 183 rice landraces of Bangladesh. Our GWASs reveal various chromosomal regions and candidate genes that are associated with different traits in Bangladeshi rice varieties. Noteworthy was the recurrent implication of chromosome 10 in all three grain‐shape‐related traits (grain length, grain width, and grain weight), indicating its pivotal role in shaping rice grain morphology. Our study also underscores the involvement of transposon gene families across these three traits. For leaf related traits, chromosome 10 was found to harbor regions that are significantly associated with leaf length and leaf width. The results of these association studies support previous findings as well as provide additional insights into the genetic diversity of rice. This is the first known GWAS study on various yield‐related traits in the varieties of Oryza sativa available in Bangladesh—the fourth largest rice‐producing country. We believe this study will accelerate rice genetics research and breeding stable high‐yielding rice in Bangladesh.
DNA barcoding of terrestrial invasive plant species in Southwest Michigan
Authors: Nath Sneha , VanSlambrouck Joshua T. , Yao Janelle W. , Gullapalli Ashika , Razi Fayyaz , Lu Yan
Published: June 2024

Because of the detrimental effects of terrestrial invasive plant species (TIPS) on native species, ecosystems, public health, and the economy, many countries have been actively looking for strategies to prevent the introduction and minimize the spread of TIPS. Fast and accurate detection of TIPS is essential to achieving these goals. Conventionally, invasive species monitoring has relied on morphological attributes. Recently, DNA‐based species identification (i.e., DNA barcoding) has become more attractive. To investigate whether DNA barcoding can aid in the detection and management of TIPS, we visited multiple nature areas in Southwest Michigan and collected a small piece of leaf tissue from 91 representative terrestrial plant species, most of which are invasive. We extracted DNA from the leaf samples, amplified four genomic loci (ITS, rbcL, matK, and trnH‐psbA) with PCR, and then purified and sequenced the PCR products. After careful examination of the sequencing data, we were able to identify reliable DNA barcode regions for most species and had an average PCR‐and‐sequencing success rate of 87.9%. We found that the species discrimination rate of a DNA barcode region is inversely related to the ease of PCR amplification and sequencing. Compared with rbcL and matK, ITS and trnH‐psbA have better species discrimination rates (80.6% and 63.2%, respectively). When ITS and trnH‐psbA are simultaneously used, the species discrimination rate increases to 97.1%. The high species/genus/family discrimination rates of DNA barcoding indicate that DNA barcoding can be successfully employed in TIPS identification. Further increases in the number of DNA barcode regions show little or no additional increases in the species discrimination rate, suggesting that dual‐barcode approaches (e.g., ITS + trnH‐psbA) might be the efficient and cost‐effective method in DNA‐based TIPS identification. Close inspection of nucleotide sequences at the four DNA barcode regions among related species demonstrates that DNA barcoding is especially useful in identifying TIPS that are morphologically similar to other species.
A Third of Organic Carbon Is Mineral Bound in Permafrost Sediments Exposed by the World's Largest Thaw Slump, Batagay, Siberia
Authors: Thomas Maxime , Jongejans Loeka L. , Strauss Jens , Vermylen Chloé , Calcus Sacha , Opel Thomas , Kizyakov Alexander , Wetterich Sebastian , Grosse Guido , Opfergelt Sophie
Published: June 2024

Organic carbon (OC) in permafrost interacts with the mineral fraction of soil and sediments, representing < 1% to ~80% of the total OC pool. Quantifying the nature and controls of mineral–OC interactions is therefore crucial for realistic assessments of permafrost‐carbon‐climate feedbacks, especially in ice‐rich regions facing rapid thaw and the development of thermo‐erosion landforms. Here, we analyzed sediment samples from the Batagay megaslump in East Siberia, and we present total element concentrations, mineralogy, and mineral–OC interactions in its different stratigraphic units. Our findings indicate that up to 34 ± 8% of the OC pool interacts with mineral surfaces or elements. Interglacial deposits exhibit enhanced OC–mineral interactions, where OC has undergone greater microbial transformation and has likely low degradability. We provide a first‐order estimate of ~12,000 tons of OC mobilized annually downslope of the headwall (i.e., the approximate mass of 30 large aircrafts), with a maximum of 38% interacting with OC via complexation with metals or associations to poorly crystalline iron oxides. These data imply that over one‐third of the OC exposed by the slump is not readily available for mineralization, potentially leading to prolonged OC residence time in soil and sediments under stable physicochemical conditions.
Pediatric pulmonology year in review—Pediatric pulmonary critical care
Authors: O'Hara Jill E. , Graham Robert J.
Published: June 2024

Pediatric pulmonary critical care literature has continued to grow in recent years. Our aim in this review is to narrowly focus on publications providing clinically‐relevant advances in pediatric pulmonary critical care in 2023.
Ignition and energy release performance of dual‐oxidant Al/MnO2/CuO ternary thermites under rapid heating conditions
Authors: Liu Zhaohu , He Chuan , Zhuang Zhihua , Li Shukui , Feng Xinya , Liu Jinxu
Published: June 2024

Tailoring the energy release performance of the thermites is crucial for their application in various fields. In this article, dual‐oxidant Al/MnO2/CuO ternary thermites with varying compositions were prepared and systematically evaluated. The ignition delay time, heat of reaction, self‐sustained burning rate, and pressure performance of the thermites were evaluated. As the Al/CuO content increased, the ignition delay time and heat of reaction decreased, while the reaction efficiency, burning rate, pressure peak, and pressurization rate increased. Furthermore, the synergistic addition of the MnO2 and CuO led to enhanced relative flame intensity and maximum flame temperature in the ternary thermite. Our work demonstrates an effective strategy for regulating the energy performance of the thermites by co‐adding of metal oxides. This approach opens avenues for tailoring thermite properties to meet the diverse requirements of various applications.
Knot or not? Identifying unknotted proteins in knotted families with sequence‐based Machine Learning model
Authors: Sikora Maciej , Klimentova Eva , Uchal Dawid , Sramkova Denisa , Perlinska Agata P. , Nguyen Mai Lan , Korpacz Marta , Malinowska Roksana , Nowakowski Szymon , Rubach Pawel , Simecek Petr , Sulkowska Joanna I.
Published: June 2024

Knotted proteins, although scarce, are crucial structural components of certain protein families, and their roles continue to be a topic of intense research. Capitalizing on the vast collection of protein structure predictions offered by AlphaFold (AF), this study computationally examines the entire UniProt database to create a robust dataset of knotted and unknotted proteins. Utilizing this dataset, we develop a machine learning (ML) model capable of accurately predicting the presence of knots in protein structures solely from their amino acid sequences. We tested the model's capabilities on 100 proteins whose structures had not yet been predicted by AF and found agreement with our local prediction in 92% cases. From the point of view of structural biology, we found that all potentially knotted proteins predicted by AF can be classified only into 17 families. This allows us to discover the presence of unknotted proteins in families with a highly conserved knot. We found only three new protein families: UCH, DUF4253, and DUF2254, that contain both knotted and unknotted proteins, and demonstrate that deletions within the knot core could potentially account for the observed unknotted (trivial) topology. Finally, we have shown that in the majority of knotted families (11 out of 15), the knotted topology is strictly conserved in functional proteins with very low sequence similarity. We have conclusively demonstrated that proteins AF predicts as unknotted are structurally accurate in their unknotted configurations. However, these proteins often represent nonfunctional fragments, lacking significant portions of the knot core (amino acid sequence).
How arginine inhibits substrate‐binding domain 2 elucidated using molecular dynamics simulations
Authors: Kienlein Maximilian , Zacharias Martin
Published: June 2024

The substrate‐binding domain 2 (SBD2) is an important part of the bacterial glutamine (GLN) transporter and mediates binding and delivery of GLN to the transporter translocation subunit. The SBD2 consists of two domains, D1 and D2, that bind GLN in the space between domains in a closed structure. In the absence of ligand, the SBD2 adopts an open conformation with larger space between domains. The GLN binding and closing are essential for the subsequent transport into the cell. Arginine (ARG) can also bind to SBD2 but does not induce closing and inhibits GLN transport. We use atomistic molecular dynamics (MD) simulations in explicit solvent to study ARG binding in the presence of the open SBD2 structure and observed reversible binding to the native GLN binding site with similar contacts but no transition to a closed SBD2 state. Absolute binding free energy simulations predict a considerable binding affinity of ARG and GLN to the binding site on the D1 domain. Free energy simulations to induce subsequent closing revealed a strong free energy penalty in case of ARG binding in contrast to GLN binding that favors the closed SBD2 state but still retains a free energy barrier for closing. The simulations allowed the identification of the molecular origin of the closing penalty in case of bound ARG and suggested a mutation of lysine at position 373 to alanine that strongly reduced the penalty and allowed closing even in the presence of bound ARG. The study offers an explanation of the molecular mechanism of how ARG competitively inhibits GLN from binding to SBD2 and from triggering the transition to a closed conformation. The proposed Lys373Ala mutation shows promise as a potential tool to validate whether a conformational mismatch between open SBD2 and the translocator is responsible for preventing ARG uptake to the cell.
Salvianolic acid B alleviates autoimmunity in Treg‐deficient mice via inhibiting IL2‐STAT5 signaling
Authors: Wang Ting , Wang Jing , Xu Huan , Yan Han , Liu Ying , Zhang Ning , Zhang Yawen , Zhang Jingmin , Xu Jingxuan , Zhang Lei , Ge Xiaolu , Meng Mingjing , Liu Peiman , Yang Qiaozhi , Qin Daogang , Li Sen , He Baokun
Published: June 2024

Regulatory T cell (Treg) deficiency leads to immune dysregulation, polyendocrinopathy, enteropathy, and X‐linked (IPEX) syndrome, which is a CD4+ T cell‐driven autoimmune disease in both humans and mice. Despite understanding the molecular and cellular characteristics of IPEX syndrome, new treatment options have remained elusive. Here, we hypothesized that salvianolic acid B (Sal B), one of the main active ingredients of Salvia miltiorrhiza, can protect against immune disorders induced by Treg deficiency. To examine whether Sal B can inhibit Treg deficiency‐induced autoimmunity, Treg‐deficient scurfy (SF) mice with a mutation in forkhead box protein 3 were treated with different doses of Sal B. Immune cells, inflammatory cell infiltration, and cytokines were evaluated by flow cytometry, hematoxylin and eosin staining and enzyme‐linked immunosorbent assay Kits, respectively. Moreover, RNA sequencing, western blot, and real‐time PCR were adopted to investigate the molecular mechanisms of action of Sal B. Sal B prolonged lifespan and reduced inflammation in the liver and lung of SF mice. Moreover, Sal B decreased plasma levels of several inflammatory cytokines, such as IL‐2, IFN‐γ, IL‐4, TNF‐α, and IL‐6, in SF mice. By analyzing the transcriptomics of livers, we determined the signaling pathways, especially the IL‐2‐signal transducer and activator of transcription 5 (STAT5) signaling pathway, which were associated with Treg deficiency‐induced autoimmunity. Remarkably, Sal B reversed the expression of gene signatures related to the IL‐2‐STAT5 signaling pathway in vitro and in vivo. Sal B prolongs survival and inhibits lethal inflammation in SF mice through the IL‐2‐STAT5 axis. Our findings may inspire novel drug discovery efforts aimed at treating IPEX syndrome.
“Sandwich” Structure (PLA/Thymol Fibre Membranes/SAP/Paper Fibre) Antibacterial Pad for Preservation of Chilled Mutton
Authors: Xu Minmin , Wu Lingling , Wang Chaozi , Saldaña Marleny D. A. , Sun Wenxiu
Published: June 2024

The antibacterial pad was developed to solve the preservation problem of chilled mutton. The antibacterial pad was a “Sandwich” structure (PLA/thymol fibre membranes/SAP/paper fibre), which could absorb water and inhibit bacteria. The fibre membranes are prepared by electrostatic spinning technology. The successful incorporation of thymol into the fibre membranes was proved by FTIR, SEM and water contact angle analysis. The release experiment showed that the fibre membranes (PLA/thymol) had a slow‐release effect, especially in fatty food simulants. According to the antibacterial experiment, the antibacterial pad had a significant inhibition effect on Escherichia coli and Staphylococcus aureus (the inhibition zone was 25 ~ 26 mm). In addition, the total viable count, total volatile alkaline nitrogen, pH value and drip loss showed that the antibacterial pads could effectively extend the shelf life of chilled mutton for 6 days. Therefore, the antibacterial pad has broad application prospects in meat preservation.
Assimilation of IASI temperature and humidity retrievals with scene‐dependent observation operators in clear‐sky scenes
Authors: Salonen Kirsti , August Thomas , Hultberg Tim , Benedetti Angela , McNally Anthony
Published: June 2024

The potential of assimilating Infrared Atmospheric Sounding Interferometer (IASI) temperature and humidity retrievals with their scene‐dependent observation operators, a product developed by the European Organisation for the Exploitation of Meteorological Satellites (EUMETSAT), has been investigated in the European Centre for Medium‐Range Weather Forecasts (ECMWF) system. The results are compared with the corresponding radiance assimilation impact. The experiments are done in a depleted observing‐system framework to emphasise the impact originating from the new data. The focus in the first assimilation experiments has been on retrievals over sea and in clear‐sky scenes, as they have high and homogeneous quality. The results demonstrate a clear statistically significant positive impact on temperature, humidity, and wind forecasts. However, the impact is somewhat smaller in magnitude for the retrieval assimilation compared with the radiance assimilation above 700 hPa.
On‐site analysis and rapid identification of citrus herbs by miniature mass spectrometry and machine learning
Authors: Wang Xingyu , Xie Yanqiao , Yu Jinliang , Chen Ye , Tian Yun , Wang Ziying , Wang Zhengtao , Li Linnan , Yang Li
Published: June 2024

Background

Natural medicines present a considerable analytical challenge due to their diverse botanical origins and complex multi‐species composition. This inherent complexity complicates their rapid identification and analysis. Tangerine peel, a product of the Citrus species from the Rutaceae family, is widely used both as a culinary ingredient and in traditional Chinese medicine. It is classified into two primary types in China: Citri Reticulatae Pericarpium (CP) and Citri Reticulatae Pericarpium Viride (QP), differentiated by harvest time. A notable price disparity exists between CP and another variety, Citri reticulatae “Chachi” (GCP), with differences being based on the original variety.

Methods

This study introduces an innovative method using portable miniature mass spectrometry for swift on‐site analysis of QP, CP, and GCP, requiring less than a minute per sample. And combined with machine learning to differentiate the three types on site, the method was used to try to distinguish GCP from different storage years.

Results

This novel method using portable miniature mass spectrometry for swift on‐site analysis of tangerine peels enabled the characterization of 22 compounds in less than one minute per sample. The method simplifies sample processing and integrates machine learning to distinguish between the CP, QP, and GCP varieties. Moreover, a multiple‐perceptron neural network model is further employed to specifically differentiate between CP and GCP, addressing the significant price gap between them.

Conclusions

The entire analytical time of the method is about 1 minute, and samples can be analyzed on site, greatly reducing the cost of testing. Besides, this approach is versatile, operates independently of location and environmental conditions, and offers a valuable tool for assessing the quality of natural medicines.
The third PLeuralEffusion And Symptom Evaluation (PLEASE‐3) study: Bendopnoea in patients with pleural effusion
Authors: Roy Bapti , Iacopetta Bianca M. , Peddle‐McInytre Carolyn J. , Donaghy Michaela , Ing Matthew , Tan Ai Ling , Lee Y. C. Gary
Published: June 2024

Background

Pleural effusions often cause disabling breathlessness, however the mechanism is unknown. Patients with pleural effusions are subjected to pleural fluid drainage on a ‘trial and error’ basis, as symptom relief varies. This population commonly complain of bendopnoea (breathlessness on bending forward) which has not been investigated. Our pilot data found bendopnoea was significantly associated with presence of pleural effusion. The PLEASE‐3 study will evaluate bendopnoea as a screening test for effusion‐related breathlessness, its predictive value of symptomatic benefits from fluid drainage and explore its underlying physiological mechanism.

Methods

PLEASE‐3 is a multi‐centre prospective study. Eligible patients are assessed at baseline (pre‐drainage) and for patients undergoing drainage, up to 72 h post‐procedure. Outcome measures include the prevalence of bendopnoea, its correlation with size of effusion and its predictive value of breathlessness relief after drainage. The relationship of bendopnoea with breathlessness, physiological parameters, functional capacity and diaphragmatic characteristics will be assessed. The study will recruit 200 participants.

Discussion

This is the first study to investigate bendopnoea in patients with pleural effusion. It has minimal exclusion criteria to ensure that the results are generalisable. The presence and clinical significance of bendopnoea in the context of pleural effusion requires thorough investigation. The post assessment of patients undergoing pleural fluid drainage will provide insight into whether the presence of bendopnoea is able to predict clinical outcomes.

Trial Registration

Name of the registry: Australia New Zealand Clinical Trial Registry

Trial registration number: ACTRN12622000465752.

URL of the trial registry record for this trial: https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=383639&isReview=true

Date of registration: Registered on 24 March 2022.

Funding of the trial: This study has received funding from the Sir Charles Gairdner Research Advisory Council research project grant. The study is sponsored by the Institute for Respiratory Health, a not‐for‐profit organisation.

Name and contact information for the trial sponsor: Mr Bi Lam; Finance manager. Level 2, 6 Verdun Street, Nedlands WA 6009. t‖ + 61 8 6151 0877 e‖ bi.lam@resphealth.uwa.edu.au

Role of sponsor: The funder is not involved in the planning of the study, gathering, analysing, and interpreting the data, or in preparing the manuscript.
Robust multitask learning in high dimensions under memory constraint
Authors: Chen Canyi , Chen Bingzhen , Kong Lingchen , Zhu Liping
Published: June 2024

We investigate multitask learning in the context of multivariate linear regression with high dimensional covariates and heavy‐tailed noise, while under the constraint of limited memory. To tackle the computational complexity arising from the non‐smoothness of the quantile loss, we reformulate it as an equivalent least squares loss, which yields robust solutions even in the presence of heavy‐tailed noise. We incorporate a group lasso penalty into the quantile loss to produce sparse solutions, and an accelerated proximal sub‐gradient descent algorithm to speed up the computation while ensuring explicit forms for penalized solutions at each iteration. The proposed algorithm is general and can be applied to similar optimization problems. Moreover, we introduce a communication‐efficient distributed algorithm that guarantees optimal convergence rates after finite communication rounds in cases where computing resources such as memory are insufficient. We also study the theoretical properties of the resultant estimate and relax the widely used model selection consistency assumption on the initial estimate. We demonstrate the effectiveness of our proposal through extensive numerical studies.
Exploring Untouched Variant of Bis(2‐methyl‐1H‐indol‐3‐yl)methane: Enhances Chemo and Mono‐Selectivity
Authors: Merneedi Ravikumar , Singh Mamata , Bharty Manoj Kumar
Published: June 2024

The new derivatives of bis(2‐methyl‐1H‐indol‐3‐yl)methane are synthesized by employing decanoic acid to boost aldehyde reactivity via electrophilic activation. The reactions entail combining 2‐methyl‐1H‐indole with various aromatic, aliphatic, and heterocyclic aldehydes at room temperature for 24 h. The newly synthesized compound 4‐(bis(2‐methyl‐1H‐indol‐3‐yl)methyl)‐3‐bromophenol f) has been characterized through 2D structure elucidation. Chemo selectivity and mono selectivity have been explored.
Bioactive Aqueous Fraction of Edible Trigonella foenum‐graecum, Piper betel, and Lagenaria siceraria Homogenate Downregulate the Inflammatory Mediators: In‐silico and In‐vitro Appraisal
Authors: Karmakar Sankha , Ikbal Abu Md Ashif , Bhardwaj Prashant , Tiwari Onkar Nath , Slama Petr , Roychoudhury Shubhadeep , Mandal Subhash C. , Kondi Vanitha , De Sirshendu , Palit Partha
Published: June 2024

Traditional nutraceutical therapy is a promising approach in the management of inflammatory disorders. Fenugreek, bottle gourd, and betel leaf are rich sources of polyphenolic secondary metabolites. They are abundantly found in the Indian subcontinent for the preparation of healthy traditional functional food. Traditional evidence recommended that these herbs could control inflammation. The study was conducted with those herbs to validate their protective role against inflammatory mediators of arthritis and asthma through in‐silico and in‐vitro models. Phytochemical tests revealed the presence of flavonoids, amino acids, polyphenols, and saponins. Molecular docking was performed against six potential inflammatory bio‐marker proteins, like, LOX‐5, 15‐LOX, PLA2, IL‐6, TNFR1 & TNF‐α with the phyto‐marker compounds of test herbs and found satisfactory binding scores against inflammatory bio‐markers. Extended studies with Fenugreek and betel leaf aqueous fractions showcased 87 % and 91 % inhibition of protein denaturation at 200 μg/ml. Bottle‐gourd and betel‐leaf demonstrated 96 % and 98 % inhibition against 15‐Lipoxygenase at 100 μg/ml. TNF‐α and IL‐6 were dropped significantly by 49 % and 36 % upon treatment of betel leaf at 200 μg/ml from the LPS‐stimulated PBMC cultured cells. Findings may recommend the development of commercial anti‐inflammatory polyherbal phytopharmaceuticals for controlling polyarthritis and inflammatory complications subject to preclinical in‐vivo and clinical investigation.
Novel Quinoline‐Based RAF Inhibitors: A Comprehensive Review on Synthesis, SAR and Molecular Docking Studies
Authors: Sahu Adarsh , Mishra Shweta , Wal Pranay , Debnath Biplab , Chouhan Deepesh , Gunjal Sachinkumar Dnyaneshwar , Tripathi Arpan Kumar
Published: June 2024

The RAF (rapidly accelerated fibrosarcoma) kinases play critical roles in a variety of different cellular processes, including the advancement of the cell cycle, the proliferation of cells, the metabolism of cells, cell migration, and the differentiation of cells. RAF kinase was thus established as an important target for the management of cancer disease. RAF inhibitors have elicited remarkable responses and enhanced survival rates in patients with BRAF‐V600E/K melanoma, but their efficacy is restricted by resistance as a result of mutations in RAF, presenting challenges in the identification of novel RAF inhibitors. This has resulted in the development of two generations of RAF inhibitors. In the past years, a variety of heterocyclic scaffolds that are capable of inhibiting RAF activity have been discovered. Quinoline, a molecule with a fused benzene ring and N‐heterocyclic pyridine, is a prime template for designing a variety of new anticancer drugs. In the last few years, quinoline derivative has been studied for their capability to inhibit RAF kinases. In this review, we have summarized synthesis, biological study, and molecular docking studies of substituted quinoline derivatives, which have shown potent anticancer activity by inhibiting the RAF kinases. The present review would help medicinal chemists streamline and guide their efforts toward developing novel quinoline‐based RAF inhibitors, which will be beneficial for drug development.
Soil Microbial Stress Responses under External Chemical and Physical Environmental Stresses
Authors: Wang Ruojun , Jin Caiyue , Qu Guangfei , Wu Fenghui , Xu Rui , Li Junyan , Liu Xinxin , Kuang Lingrui , Yang Jieqian , Tian Yaxin
Published: June 2024

Soil microorganisms play a crucial role in maintaining soil ecosystem health. Their metabolic processes are directly impacted by various environmental stresses caused by the increasing release of chemical pollutants and changes in the physical environment due to rapid societal development. This paper aimed to investigate the mechanisms underlying the changes in soil microbial stress responses under various external environmental stresses. The impact of pollutants on soil ecological structure was analyzed by summarizing the stress response patterns of soil microorganisms to inorganic pollutants, organic pollutants, and extreme physical environmental factors. Additionally, the migration and transformation behaviors of various complex pollutants, facilitated by the involvement of soil microorganisms, were investigated. Moreover, a novel approach was proposed for pollutant control, suggesting that manipulating the external physical field of a certain intensity could guide microbial communities and their functions towards controllable evolution within the soil environment. Therefore, this paper was essential for exploring the diversity of soil microbial stress responses, strategically regulating contaminant transport, mitigating risks associated with soil complexity, and ultimately reshaping soil ecological functions.
Bis‐Ureido‐Substituted Benzenesulfonamides: Evaluation of Their Antibacterial, Anticholinesterase, and Cytotoxicity Properties
Authors: Tekeli Tuba , Lolak Nebih , Tekeli Yener , Bozgeyik Esra , Anakok Deniz Akin , Çete Servet , Gülçin Ilhami , Akocak Suleyman
Published: June 2024

In this study, we present the re‐synthesis of a series of twelve bis‐ureido‐substituted benzenesulfonamides, focusing on their potential as antibacterial, anticholinesterase, and cytotoxic agents. First, the antibacterial assessment of these compounds indicated varying activity levels across different bacterial strains, with S. aureus displaying resistance to all compounds, while compounds 9 and 11 exhibited promise against E. faecalis with a MIC value of 31.25 μg/mL. Additionally, P. aeruginosa showed resistance to compounds containing 4‐aminobenzene sulfonamides, whereas derivatives such as (8–11) and compound 19 displayed notable activity against E. coli, comparable to Ampicillin. Second, their anticholinesterase activities were examined, with a focus on their potential role in addressing neurological disorders, particularly Alzheimer′s disease. The findings indicated that all synthesized compounds showed a significant inhibitory effect on both AChE and BChE enzymes. Compound 11 demonstrated the most effective inhibition on the AChE enzyme with an IC50 value of 0.2160±0.09 nM, while compound 18 exhibited the most potent inhibition on the BChE enzyme with an IC50 value of 0.2257±0.06 nM. Finally, cytotoxicity studies were conducted across various cell lines, including breast, lung, and prostate cancer cells and normal cells. The results revealed that compound 12 emerged as the most potent tested compound against breast cancer cells with no cytotoxic effect on CRL‐4010 normal breast epithelial cells. The research presented here not only highlights the multifaceted pharmacological potential of bis‐ureido‐substituted benzenesulfonamides, but also indicates their potential as versatile compounds for antibacterial, anticholinesterase, and cytotoxicity applications, opening up new avenues for drug discovery and development.
One‐Pot Three‐Component Construction of 2,4‐Diarylbenzo[4,5] thieno[3,2‐d] pyrimidines Using Elemental Sulfur as a Sulfur Source
Authors: Li Guorui , Wen Fei , Li Zheng
Published: June 2024

An efficient method for the construction of 2,4‐diarylbenzo[4,5]thieno[3,2‐d]pyrimidines through the base‐promoted one‐pot three‐component tandem reactions of o‐nitrochalcones, benzamidine hydrochlorides, and elemental sulfur is described. The salient features of this protocol are the use of cheap and abundant sulfur source, readily available starting materials, transition‐metal‐free and mild conditions, satisfactory yield, and simple workup procedures. This transformation can also carry out on gram scale.