bluuebunny/crossref_metadata_2025 huggingface dataset:
Proteomic profiling of human plasma extracellular vesicles identifies PF4 and C1R as novel biomarker in sarcopenia
Authors: Aparicio Paula , Navarrete‐Villanueva David , Gómez‐Cabello Alba , López‐Royo Tresa , Santamaría Enrique , Fernández‐Irigoyen Joaquín , Ausín Karina , Arruebo Manuel , Sebastian Victor , Vicente‐Rodríguez Germán , Osta Rosario , Manzano Raquel
Published: July 2024

Background

Sarcopenia, the gradual and generalized loss of muscle mass and function with ageing, is one of the major health problems in older adults, given its high prevalence and substantial socioeconomic implications. Despite the extensive efforts to reach consensus on definition and diagnostic tests and cut‐offs for sarcopenia, there is an urgent and unmet need for non‐invasive, specific and sensitive biomarkers for the disease. Extracellular vesicles (EVs) are present in different biofluids including plasma, whose cargo reflects cellular physiology. This work analysed EV proteome in sarcopenia and robust patients in the search for differentially contained proteins that can be used to diagnose the disease.

Methods

Plasma small EVs (sEVs) from a total of 29 robust controls (aged 73.4 ± 5.6 years; 11 men and 18 women) and 49 sarcopenic patients (aged 82.3 ± 5.4 years; 15 men and 34 women) aged 65 years and older were isolated and their cargo was analysed by proteomics. Proteins whose concentration in sEVs was different between sarcopenic and robust patients were further validated using ELISA. The concentration of these candidates was correlated to the EWGSOP2 sarcopenia tests for low muscle strength and low physical performance, and receiver operating characteristic (ROC) curve analyses were carried out to evaluate their diagnostic power, sensitivity and specificity.

Results

Proteomic analysis identified 157 sEVs proteins in both sarcopenic and robust samples. Among them, 48 proteins had never been reported in the ExoCarta nor Vesiclepedia databases. Statistical analysis revealed eight proteins whose concentration was significantly different between groups: PF4 (log2 FC = 4.806), OIT3 (log2 FC = −1.161), MMRN1 (log2 FC = −1.982), MASP1 (log2 FC = −0.627), C1R (log2 FC = 1.830), SVEP1 (log2 FC = 1.295), VCAN (FC = 0.937) and SPTB (log2 FC = 1.243). Among them, platelet factor 4 (PF4) showed the lowest concentration while Complement C1r subcomponent (C1R) increased the most in sarcopenic patients, being these results confirmed by ELISA (P = 1.07E‐09 and P = 0.001287, respectively). The concentrations of candidate proteins significantly correlated with EWGSOP2 tests currently used. ROC curve analysis showed an area under the curve of 0.8921 and 0.7476 for PF4 and C1R, respectively. Choosing the optimal for PF4, 80% sensitivity and 85.71% specificity was reached while the optimal cut‐off value of C1R would allow sarcopenia diagnosis with 75% sensitivity and 66.67% specificity.

Conclusions

Our results support the determination of EV PF4 and C1R as plasma diagnostic biomarkers in sarcopenia and open the door to investigate the role of the content of these vesicles in the pathogeny of the disease.
Pregnant individuals' genetic literacy and decisional conflict about prenatal screening tests: A cross‐sectional study
Authors: Yeşilçinar İlknur , Şahin Eda , Tutar Sadettin Oğuzhan
Published: July 2024

Understanding the prenatal screening and diagnostic tests performed during pregnancy and making a decision in line with the test results can be a complex process for pregnant individuals and their families. Therefore, this study examined pregnant individuals' genetic literacy and decisional conflict regarding prenatal screening tests. The study was conducted with 328 pregnant individuals who applied to a training and research hospital to receive antenatal care between April 05 and September 30, 2021. Research data were collected by using the “Decisional Conflict Scale,” “SURE Scale,” and “Genetic Literacy and Comprehension Measure.” The mean age of the participants was 28.69 ± 5.48, and the mean gestational week was 25.90 ± 10.43. A statistically significant difference was found between the educational levels of the pregnant individuals and the genetic literacy and comprehension scales (p < 0.001). A statistically significant difference was found between getting information about prenatal screening tests, having a screening test and decisional conflict scale, SURE Scale, and genetic literacy and comprehension scales (p < 0.001). A weak, negative, statistically significant correlation was found between the genetic literacy and comprehension familiarity and decision conflict scales (r = −0.177, p = 0.001). It is well known that pregnant individuals have difficulty understanding and interpreting test results due to prenatal screening tests that include genetic information. In our study, approximately half of the pregnant individuals received information about prenatal screening tests. Therefore, prenatal care must include the necessary information about prenatal screening tests. The study found that as the genetic literacy of pregnant individuals increased, the conflict of decisions they experienced decreased. Accordingly, it is suggested that interventions to increase genetic literacy among pregnant individuals may be effective in reducing decisional conflict regarding prenatal screening tests.
Inefficient tissue immune response against MPXV in an immunocompromised mpox patient
Authors: Matschke Jakob , Hartmann Kristin , Pfefferle Susanne , Wang Yue , Valdes Pablo A. , Thies Edda , Schweizer Michaela , Lütgehetmann Marc , Schmiedel Stefan , Bernreuther Christian , Boyden Edward S. , Glatzel Markus , Krasemann Susanne
Published: July 2024

The recent outbreak of monkeypox virus (MPXV) was unprecedented in its size and distribution. Those living with uncontrolled HIV and low CD4 T cell counts might develop a fulminant clinical mpox course with increased mortality, secondary infections, and necrotizing lesions. Fatal cases display a high and widespread MPXV tissue burden. The underlying pathomechanisms are not fully understood. We report here the pathological findings of an MPXV‐driven abscess in gastrocnemius muscle requiring surgery in an immunocompromised patient with severe mpox. Presence of virus particles and infectivity were confirmed by electron microscopy, expansion microscopy, and virus culture, respectively. MPXV tissue distribution by immunohistochemistry (IHC) showed a necrotic core with infection of different cell types. In contrast, at the lesion rim fibroblasts were mainly infected. Immune cells were almost absent in the necrotic core, but were abundant at the infection rim and predominantly macrophages. Further, we detected high amounts of alternatively activated GPNMB+‐macrophages at the lesion border. Of note, macrophages only rarely colocalized with virus‐infected cells. Insufficient clearance of infected cells and infection of lesion‐associated fibroblasts sustained by the abundance of profibrotic macrophages might lead to the coalescing of lesions and the severe and persistent clinical mpox course observed in immunocompromised patients.
An approaching method based on integral for linear neutral delay differential equations by using Hermite polynomials
Authors: Yüzbaşı Şuayip , Karaağaçlı Özlem
Published: July 2024

This article presents a approximation method for linear neutral delay differential equations using Hermite polynomials. The method ensures the unknown function to be found by approximating the first derivative with the help of the finite Hermite series. This method reduces the problem to a linear algebraic system using the first derivative approach, matrix operations and collocation points. Also error of the solution is estimated by constructing an error problem. Numerical examples are solved to explain the method and error estimation technique. The results demonstrate the effectiveness and accuracy of the current study. Calculations have been made using MATLAB.
Favourable clinical outcomes and low revision rate after M‐ACI in adolescents with immature cartilage compared to adult controls: Results at 10 years
Authors: Weishorn Johannes , Wiegand Johanna , Koch Kevin‐Arno , Trefzer Raphael , Renkawitz Tobias , Walker Tilman , Bangert Yannic
Published: July 2024

Purpose

The purpose of this study was to evaluate long‐term survival, patient‐reported outcomes (PROs) and radiographic results of matrix‐associated autologous chondrocyte implantation (M‐ACI) in adolescents with immature cartilage and compare them to adult controls.

Methods

A retrospective matched‐pair analysis was performed comparing the PRO after M‐ACI for focal cartilage defect of the knee in cartilaginous immature adolescents to mature adults. Groups were matched for sex, body mass index, defect site and size, symptom duration and the number of previous knee surgeries. Knee Injury and Osteoarthritis Outcome Score (KOOS) and the Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART 2.0) scores were assessed at least 60 months postoperatively. Patient acceptable symptomatic state (PASS) and clinical response rate in KOOS and KOOS subscores were calculated.

Results

A total of 54 patients were matched. At a mean of 96 months (65–144 months), no surgical complications, graft hypertrophy or reoperations were noted in the cohorts studied. Adolescents showed superior PROs at the final follow‐up (76.9 ± 14.1 vs. 66.4 ± 15.0, p = 0.03) and were significantly more likely to achieve PASS (74.1% vs. 55.6%; p = 0.02) compared to the adult cohort. The KOOS subscale analysis showed long‐term benefits for adolescents in terms of symptom improvement, pain reduction, activities of daily living, sports and quality of life (p < 0.05). None of the patients in the adolescent group showed graft hypertrophy on magnet resonance imaging or signs of osteoarthritis on radiographs at long‐term follow‐ups.

Conclusions

M‐ACI is an effective treatment for chondral defects of the knee in patients with immature cartilage with low revision rates and high patient satisfaction over the long term. Adolescents showed comparable clinical and radiographic results in the short and medium term, with slightly more favourable, clinically relevant functional results in adolescents in the long term. M‐ACI can be safely used in adolescents, and consideration should be given to expanding the indication to include these patients.

Level of Evidence

Level III.
Ligament augmentation and reconstruction system (LARS) synthetic grafts are safe and effective for medial collateral ligament and posterolateral corner reconstructions in elite athletes
Authors: Jones Mary , Pinheiro Vitor H. , Church J. Samuel , Ball Simon V. , Williams Andy
Published: July 2024

Purpose

This study documents the efficacy and safety of using a Ligament Augmentation and Reconstruction System (LARS) ligament graft to augment extra‐articular knee ligament reconstructions in elite athletes by reporting return‐to‐play (RTP) rates and levels, career longevity and complications.

Methods

A consecutive series of all extra‐articular knee ligament reconstructions augmented by LARS ligaments in elite athletes undertaken by three specialist sports knee surgeons between 2013 and 2020 were reviewed. Seventy‐six elite athletes, aged over 16 years old, and more than 2 years postsurgery were included. RTP was defined as competing at professional level or national/international level in amateur sport.

Results

There were 64 medial collateral ligament (MCL) and 12 posterolateral corner (PLC) reconstructions. Fifty‐two (68.4%) underwent concomitant autograft cruciate ligament(s) reconstruction. The mean age was 25.1 years (SD ± 4.5). Most were football (35, 46.1%) or rugby players (35, 46.1%). Sixty‐seven athletes (88.2%) RTP with 65 (97.0%) of these playing at the same or higher Tegner level. Fifty‐six (83.6%) of the athletes that RTP were still playing at 2 years postsurgery. Twenty (57.1%) of those who had RTP and were more than 5 years postsurgery were still playing at 5 years. Six (7.9%) players required further surgery relating to the LARS/metalwork. One case had soft tissue inflammation adjacent to the proximal end of the synthetic graft, but it is unknown if this was mechanical irritation or a biological reaction. One MCL reruptured 4 years after RTP.

Conclusion

Utilising LARS to augment extra‐articular knee ligament reconstructions allows 88.2% of athletes with a variety of knee ligament injuries to return to elite sport. The low morbidity rates coupled with 57% of athletes still playing 5 years postsurgery demonstrates that the LARS is safe and effective in these cases. Although there are reports of LARS ligaments being used in MCL and PLC reconstructions, there is very little evidence investigating if they are safe and effective. This study demonstrates that LARS synthetic grafts can be safely used for MCL and PLC reconstructions in elite athletes and they permit a high RTP with a low risk of complications.

Level of Evidence

Level IV.
Increased combined anteversion is associated with larger posterior acetabular rim ossification in patients with femoroacetabular impingement syndrome
Authors: Zhang Hongguang , Zhang Siqi , Zhou Guangjin , Xu Yan
Published: July 2024

Purpose

(1) To determine the prevalence, magnitude and distribution pattern of acetabular rim ossification in patients with femoroacetabular impingement syndrome (FAIS) and (2) to determine the association between acetabular rim ossification and rotational abnormalities of the hip.

Methods

Patients underwent hip arthroscopic surgery for FAIS at our institute between January 2021 and May 2022 were retrospectively reviewed. Patients were included if preoperative computed tomography (CT) images of the operated hip and ipsilateral distal femur were available for the measurement of femoral and acetabular anteversion. The presence and size of acetabular rim ossification were evaluated on coronal CT sections for the superior half of the acetabulum on each clockface location. The associations between acetabular rim ossification and radiographic parameters of hip rotational morphology were examined.

Results

A total of 214 hips were included. Acetabular rim ossification was found in 167 hips (78%) and the most common locations were 10 and 11 o'clock. Patients presenting with acetabular rim ossification had a mean size of 4.6 ± 1.6 mm. It was the largest at 9 o'clock position (4.9 ± 2.2 mm), with a decreasing trend in size from posterior to anterior. Logistics regression analysis found age was associated with the occurrence of posterior ossification (p = 0.002). Linear regression analysis found age (p = 0.049) and male sex (p < 0.001) were significantly correlated with the size of ossification. Patients with increased cranial combined anteversion had larger posterior ossification than patients with normal and decreased cranial combined anteversion (4.2 ± 2.9 vs. 3.1 ± 2.5 mm, p = 0.016; 4.2 ± 2.9 vs. 2.5 ± 2.4 mm, p = 0.005).

Conclusion

Increased combined anteversion is associated with greater posterior acetabular rim ossification. The presence and size of acetabular rim ossification are positively associated with older age and male sex.

Level of Evidence

Level III.
Treatment of Iron‐Induced Cutaneous Hyperpigmentation With Energy‐Based Devices
Authors: Sharma Ajay N. , Golbari Nicole M. , Grushchak Solomiya , Andrade Adriana Ribas , Zachary Christopher B.
Published: July 2024

Objectives

Iatrogenic cutaneous siderosis is a well‐recognized dermatologic complication after parenteral iron infusion. The condition manifests as discrete, hyperpigmented patches near the site of injection. Most cases do not resolve spontaneously, leading to significant aesthetic and psychological distress to patients. A recent case of iatrogenic cutaneous siderosis at our institution prompted a systematic review of the efficacy of energy‐based devices previously reported in the treatment of this condition.

Methods

PubMed and Cochrane databases were searched for all peer‐reviewed articles published using the following search terms: “iron OR heme OR hemosiderosis OR siderosis” and “hyperpigmentation OR staining OR tattoo.” Articles reporting on energy‐based devices in the treatment of iron‐induced hyperpigmentation were included.

Results

A total of seven articles and 54 total patients were included in this review. All patients, including the patient treated at our institution, were female, with an average age of 44 years. Hyperpigmentation was most commonly associated with intravenous iron infusion (48/54, 89%), on the arm or forearm (44/54, 81%), and used for the treatment of underlying iron deficiency anemia (54/54, 100%). The application of six different nanosecond or picosecond quality‐switched laser systems was reported in the treatment of cutaneous siderosis, with wavelengths ranging from 532 to 1064 nm. Spot sizes varied between 2 and 7 mm, with energy fluences spanning 0.5–40 J/cm2 depending on both the device and spot size. Outcomes were measured after an average of 5.4 laser treatments and 10.4 months, with over half of all reported patients experiencing complete clearance (27/50, 54%). Our patient received treatment in three test areas with picosecond alexandrite 785 nm, nanosecond Nd:YAG 532 nm, and picosecond Nd:YAG 532 nm devices. The nanosecond Nd:YAG 532 nm treated area demonstrated the greatest improvement, and the entire arm was subsequently treated with this device.

Conclusions

Despite the often intractable nature of iatrogenic cutaneous siderosis, laser surgery is a reasonable and safe treatment modality for patients seeking cosmetic improvement of this dyschromia. Dermatologists should be aware of this entity and the efficacy of the energy‐based devices currently in our armamentarium. A combination approach may need to be utilized with different wavelengths and pulsed widths to target iron pigment in both dermal and subcutaneous layers.
The Hartogs–Lindenbaum spectrum of symmetric extensions
Authors: Ryan‐Smith Calliope
Published: July 2024

We expand the classic result that is equivalent to the statement “For all , ” by proving the equivalence of many more related statements. Then, we introduce the Hartogs–Lindenbaum spectrum of a model of , and inspect the structure of these spectra in models that are obtained by a symmetric extension of a model of . We prove that all such spectra fall into a very rigid pattern.
Development of Macromolecular Cryoprotectants for Cryopreservation of Cells
Authors: Yuan Liang , Chen Binlin , Zhu Kongying , Ren Lixia , Yuan Xiaoyan
Published: July 2024

Cryopreservation is a common way for long‐term storage of therapeutical proteins, erythrocytes, and mammalian cells. For cryoprotection of these biosamples to keep their structural integrity and biological activities, it is essential to incorporate highly efficient cryoprotectants. Currently, permeable small molecular cryoprotectants such as glycerol and dimethyl sulfoxide dominate in cryostorage applications, but they are harmful to cells and human health. As acting in the extracellular space, membrane‐impermeable macromolecular cryoprotectants, which exert remarkable membrane stabilization against cryo‐injury and are easily removed post‐thaw, are promising candidates with biocompatibility and feasibility. Water‐soluble hydroxyl‐containing polymers such as poly(vinyl alcohol) and polyol‐based polymers are potent ice recrystallization inhibitors, while polyampholytes, polyzwitterions, and bio‐inspired (glyco)polypeptides can significantly increase post‐thaw recovery with reduced membrane damages. In this review, the synthetic macromolecular cryoprotectants are systematically summarized based on their synthesis routes, practical utilities, and cryoprotective mechanisms. It provides a valuable insight in development of highly efficient macromolecular cryoprotectants with valid ice recrystallization inhibition activity for highly efficient and safe cryopreservation of cells.
Identifying numerical bifurcation structures of codimensions 1 and 2 in interacting species system
Authors: Dutta Swagata , Mandal Gourav , Narayan Guin Lakshmi , Chakravarty Santabrata
Published: July 2024

The present study has focused on the examination of a Holling type III nonlinear mathematical model that incorporates the influence of fear and Michaelis–Menten‐type predator harvesting. The incorporation of fear with respect to the prey species has been observed to result in a reduction in the survival probability of the prey population and a concurrent reduction in the reproduction rate of the prey species. The existence and stability of ecologically significant equilibria have been ascertained through mathematical analysis. Emphasis within the proposed model primarily centers on numerical bifurcations of codimensions 1 and 2. Numerical validation has been performed on all simulated outcomes within the feasible range of parametric values. Dynamical characteristics of the model have subsequently undergone investigation through a series of numerical simulations, successfully revealing various forms of local and global bifurcations. In addition to the identification of saddle‐node, Hopf, Bogdanov–Takens, transcritical, cusp, homoclinic, and limit point cycle (LPC) bifurcations, the model has also demonstrated bistability and global asymptotic stability. These bifurcation phenomena serve as illustrative examples of the intricate dynamical behavior inherent to the model. Numerical validation through graphical representations has been utilized to elucidate the effects of factors such as fear, nonlinear predator harvesting, and predation rate on the dynamics of the interacting species under different parametric conditions.
Reduced B0/B1+ sensitivity in velocity‐selective inversion arterial spin labeling using adiabatic refocusing pulses
Authors: Bolar Divya S. , Barnes Ryan A. , Chen Conan , Han Fei , Pfeuffer Josef , Liu Thomas T. , Wong Eric C.
Published: July 2024

Purpose

To mitigate the B0/B1+ sensitivity of velocity‐selective inversion (VSI) pulse trains for velocity‐selective arterial spin labeling (VSASL) by implementing adiabatic refocusing. This approach aims to achieve artifact‐free VSI‐based perfusion imaging through single‐pair label‐control subtractions, reducing the need for the currently required four‐pair dynamic phase‐cycling (DPC) technique when using a velocity‐insensitive control.

Methods

We introduce a Fourier‐transform VSI (FT‐VSI) train that incorporates sinc‐modulated hard excitation pulses with MLEV‐8‐modulated adiabatic hyperbolic secant refocusing pairs. We compare performance between this train and the standard composite refocusing train, including with and without DPC, for dual‐module VSI VSASL. We evaluate (1) simulated velocity‐selective profiles and subtraction fidelity across a broad B0/B1+ range, (2) subtraction fidelity in phantoms, and (3) image quality, artifact presence, and gray‐matter perfusion heterogeneity (as measured by the spatial coefficient of variation) in healthy human subjects.

Results

Adiabatic refocusing significantly improves FT‐VSI robustness to B0/B1+ inhomogeneity for a single label‐control subtraction. Subtraction fidelity is dramatically improved in both simulation and phantoms compared with composite refocusing without DPC, and is similar compared with DPC methods. In humans, marked artifacts seen with the non‐DPC composite refocusing approach are eliminated, corroborated by significantly reduced gray‐matter heterogeneity (via lower spatial coefficient of variation values).

Conclusion

A novel VSASL labeling train using adiabatic refocusing pulses for VSI was found to reduce artifacts related to B0/B1+ inhomogeneity, thereby providing an alternative to DPC and its associated limitations, which include increased vulnerability to physiological noise and motion, reduced functional MRI applicability, and suboptimal data censoring.
A multiobjective optimization framework for site investigation program based on Bayesian approach and NSGA‐II
Authors: Sun Yang , Xu Ziying , Sun Jinshan , Chen Zhen
Published: July 2024

Site investigation provides essential geotechnical parameter information for analysis and design. However, three conflicting objectives, namely exploration effort, robustness and parameter uncertainty, pose a challenge to the development of an optimal site investigation program. In this study, a three objective optimization framework for the site investigation program is proposed based on the Bayesian approach and the non‐dominated sorting genetic algorithm (NSGA‐II). The only inputs required by the proposed framework are prior distribution of geotechnical parameters and error information. The prior distribution of geotechnical parameters is derived from integrating engineering experience and measurements from basic exploration boreholes. The error information is obtained based on literature and expert judgment related to the specific project. Firstly, a design pool of candidate investigation programs is generated using Bayesian approach to determine the locations and number of exploration boreholes. The NSGA‐II is then applied to identify the optimal program that balances lower cost, higher robustness, and lower uncertainty. The proposed multiobjective optimization framework is illustrated and validated through a real site investigation case in Chongqing, China, aimed at determining the ultimate bearing capacity of the rock foundation. The spatial correlation of parameters within the study area is also considered. The optimal program is represented by the location and number of exploration boreholes. By comparing measurements with predictions from different site investigation programs, the efficiency of the proposed multiobjective framework is demonstrated. Additionally, the influence of engineering experience and random field modeling on the investigation program is discussed.
The AUA/SUFU guideline on the diagnosis and treatment of idiopathic overactive bladder
Authors: Cameron Anne P. , Chung Doreen E. , Dielubanza Elodi J. , Enemchukwu Ekene , Ginsberg David A. , Helfand Brian T. , Linder Brian J. , Reynolds W. Stuart , Rovner Eric S. , Souter Lesley , Suskind Anne M. , Takacs Elizabeth , Welk Blayne , Smith Ariana L.
Published: July 2024

Purpose

The purpose of this guideline is to provide evidence‐based guidance to clinicians of all specialties on the evaluation, management, and treatment of idiopathic overactive bladder (OAB). The guideline informs the reader on valid diagnostic processes and provides an approach to selecting treatment options for patients with OAB through the shared decision‐making process, which will maximize symptom control and quality of life, while minimizing adverse events and burden of disease.

Methods

An electronic search employing OVID was used to systematically search the MEDLINE and EMBASE databases, as well as the Cochrane Library, for systematic reviews and primary studies evaluating diagnosis and treatment of OAB from January 2013 to November 2023. Criteria for inclusion and exclusion of studies were based on the Key Questions and the populations, interventions, comparators, outcomes, timing, types of studies and settings (PICOTS) of interest. Following the study selection process, 159 studies were included and were used to inform evidence‐based recommendation statements.

Results

This guideline produced 33 statements that cover the evaluation and diagnosis of the patient with symptoms suggestive of OAB; the treatment options for patients with OAB, including Noninvasive therapies, pharmacotherapy, minimally invasive therapies, invasive therapies, and indwelling catheters; and the management of patients with BPH and OAB.

Conclusion

Once the diagnosis of OAB is made, the clinician and the patient with OAB have a variety of treatment options to choose from and should, through shared decision‐making, formulate a personalized treatment approach taking into account evidence‐based recommendations as well as patient values and preferences.
A two‐stage adaptive robust model for designing a reliable blood supply chain network with disruption considerations in disaster situations
Authors: Qing Ling , Yin Yunqiang , Wang Dujuan , Yu Yugang , Cheng T. C. E.
Published: July 2024

We consider multi‐period blood supply chain network design in disaster situations that involve blood donor groups, permanent and temporary blood collection facilities, blood banks, and hospitals. We use a discrete scenario set to model the uncertain blood supply and demand, and the unforeseeable disruptions in permanent blood collection facilities, blood banks, and road links arising from a disaster, where instead of complete failure, disrupted permanent blood collection facilities and blood blanks may only lose part of their capacities. To design a reliable blood supply network to mitigate the possible disruptions, we present a two‐stage adaptive robust model that integrates the location, inventory, and allocation decisions incorporating a blood sharing strategy, where blood can be delivered from a disrupted/non‐disrupted blood bank to disrupted blood banks to enhance the flexibility of the relief network. For this novel problem, we devise an exact algorithm that integrates column‐and‐constraint generation and Benders decomposition and introduce several non‐trivial acceleration techniques to speed up the solution generation process. We conduct extensive numerical studies on random data sets to evaluate the algorithmic performance. We also conduct a case study in Tehran to demonstrate its real‐life applicability and examine the impacts of key model parameters on the solutions. The numerical results verify the benefits of our model over typical benchmarks, that is, deterministic and stochastic models, and the superiority of our solution algorithm over the CPLEX solver and two well‐known solution approaches, that is, column‐and‐constraint generation and Benders decomposition. Finally, based on the numerical results, we derive managerial insights from the analytical findings.
Hearing, Balance, and Mortality: Sex‐Specific Patterns in a Longitudinal Study
Authors: Berge Jan E. , Nilsen Geir A. , Goplen Frederik K. , Kringeland Ester , Nordahl Stein H. G. , Aarstad Hans J.
Published: July 2024

Objectives

Assess the association of hearing on sex‐specific overall mortality and death from acute cardiovascular disease and evaluate if these effects are modulated by postural balance.

Study Design

Cohort study.

Setting

Otolaryngology department at an academic hospital.

Methods

Patients underwent standard clinical examination, laboratory examination including stabilometry and audiometry. Pure tone average on the best hearing ear was calculated from 0.5, 1, 2, and 3 kHz. Cause of death was retrieved from the Norwegian Cause of Death Registry.

Results

A total of 1036 patients (58.8% women) were followed for 26 ± 3 years. In Cox regression analyses for overall mortality adjusted for age, past medical history, and vestibular disease, 10 dB increase in hearing threshold was associated with a 14% increase in mortality among men (hazard ratio 95% confidence interval: 1.02‐1.28, P = .02), but no significant association was seen between hearing and mortality in women (0.92‐1.15, P = .60). The same analyses for acute cardiovascular death found that a 10 dB increase in hearing threshold was associated with a 57% increase in hazard ratio in men (1.21‐2.05, P < .001), but no significant effect of hearing on survival was seen in women (P = .71). Adjusting for postural balance did not change the association between hearing and mortality.

Conclusion

This study finds hearing threshold is associated with overall mortality and acute cardiovascular death among men, with no such association observed among women. Our findings indicate important differences between men and women and suggest that such differences should be taken into consideration in audiological research.
Review on electrospray nanoparticles for drug delivery: Exploring applications
Authors: Patel Pratikshkumar R. , Haemmerich Dieter
Published: July 2024

Electrospraying has emerged as a versatile technique in the pharmaceutical field due to its potential in drug delivery and formulation. With its advantages of cost‐effectiveness, reproducibility, ease of operation, and scalability, electrospraying offers numerous benefits for pharmaceutical applications. Notably, the production of nanoparticles using electrospraying provides unique properties, including small size, drug encapsulation capabilities, biocompatibility, and scalability. Electrospray nanoparticles have demonstrated significant promise in various drug delivery routes, such as oral and topical administration. These nanoparticles enhance drug stability, protection, and permeability, effectively overcoming limitations associated with these routes. Moreover, electrospray nanoparticles have proven valuable in targeted drug delivery, improving drug bioavailability and efficacy. Their ability to penetrate tissues and cells enables enhanced drug delivery to specific sites within the body. Additionally, electrospray nanoparticles can be tailored with targeting ligands or responsive components for controlled release and combination therapy, exhibiting successful applications in cancer treatment and neurological disorders. Therefore, electrospray nanoparticle technology shows great promise in biomedical applications, offering a versatile platform for targeted drug delivery and therapeutic interventions. This comprehensive review examines the various drug delivery applications of electrospraying and provides insights into its possibilities and challenges. The paper discusses the principles, methods, and parameters of electrospraying, while also exploring its use in fabricating drug delivery systems, addressing poorly soluble drugs. By synthesizing the findings from multiple studies, this review offers a comprehensive understanding of electrospraying's current state and potential in the pharmaceutical industry.
Pseudophosphorylation of single residues of the J‐domain of DNAJA2 regulates the holding/folding balance of the Hsc70 system
Authors: Velasco‐Carneros Lorea , Bernardo‐Seisdedos Ganeko , Maréchal Jean‐Didier , Millet Oscar , Moro Fernando , Muga Arturo
Published: July 2024

The Hsp70 system is essential for maintaining protein homeostasis and comprises a central Hsp70 and two accessory proteins that belong to the J‐domain protein (JDP) and nucleotide exchange factor families. Posttranslational modifications offer a means to tune the activity of the system. We explore how phosphorylation of specific residues of the J‐domain of DNAJA2, a class A JDP, regulates Hsc70 activity using biochemical and structural approaches. Among these residues, we find that pseudophosphorylation of Y10 and S51 enhances the holding/folding balance of the Hsp70 system, reducing cochaperone collaboration with Hsc70 while maintaining the holding capacity. Truly phosphorylated J domains corroborate phosphomimetic variant effects. Notably, distinct mechanisms underlie functional impacts of these DNAJA2 variants. Pseudophosphorylation of Y10 induces partial disordering of the J domain, whereas the S51E substitution weakens essential DNAJA2‐Hsc70 interactions without a large structural reorganization of the protein. S51 phosphorylation might be class‐specific, as all cytosolic class A human JDPs harbor a phosphorylatable residue at this position.
Multiple Functional Protein–Protein Interaction Interfaces Allosterically Regulate ATP‐Binding in Cyclin‐Dependent Kinase‐1
Authors: Vishwakarma Krishna Kant , Kolthur Ullas Seetharam , Venkatramani Ravindra
Published: July 2024

The ATP‐dependent phosphorylation activity of cyclin‐dependent kinase 1 (CDK1), an essential enzyme for cell cycle progression, is regulated by interactions with Cyclin‐B, substrate, and Cks proteins. We have recently shown that active site acetylation in CDK1 abrogated binding to Cyclin‐B which posits an intriguing long‐range communication between the catalytic site and the protein–protein interaction (PPI) interface. Now, we demonstrate a general allosteric link between the CDK1 active site and all three of its PPI interfaces through atomistic molecular dynamics (MD) simulations. Specifically, we examined ATP binding free energies to CDK1 in native nonacetylated (K33wt) and acetylated (K33Ac) forms as well as the acetyl‐mimic K33Q and the acetyl‐null K33R mutant forms, which are accessible in vitro. In agreement with experiments, ATP binding is stronger in K33wt relative to the other three perturbed states. Free energy decomposition reveals, in addition to expected local changes, significant and selective nonlocal entropic responses to ATP binding/perturbation of K33 from the ‐helix, activation loop (A‐loop), and ‐H segments in CDK1 which interface with Cyclin‐B, substrate, and Cks proteins, respectively. Statistical analysis reveals that while entropic responses of protein segments to active site perturbations are on average correlated with their dynamical changes, such correlations are lost in about 9%–48% of the dataset depending on the segment. Besides proving the bi‐directional communication between the active site and the CDK1:Cyclin‐B interface, our study uncovers a hitherto unknown mode of ATP binding regulation by multiple PPI interfaces in CDK1.
Unveiling the diet of two generalist stink bugs, Halyomorpha halys and Pentatoma rufipes (Hemiptera: Pentatomidae), through metabarcoding of the ITS2 region from gut content
Authors: Berteloot Olivier Hendrik , Peusens Gertie , Beliën Tim , De Clercq Patrick , Van Leeuwen Thomas
Published: July 2024

BACKGROUND

The use of DNA metabarcoding has become an increasingly popular technique to infer feeding relationships in polyphagous herbivores and predators. Understanding host plant preference of native and invasive herbivore insects can be helpful in establishing effective integrated pest management (IPM) strategies. The invasive Halyomorpha halys and native Pentatoma rufipes are piercing‐sucking stink bug pests that are known to cause economic damage in commercial fruit orchards.

RESULTS

In this study, we performed molecular gut content analysis (MGCA) on field‐collected specimens of these two herbivorous pentatomids using next‐generation amplicon sequencing (NGAS) of the internal transcribed spacer 2 (ITS2) barcode region. Additionally, a laboratory experiment was set up where H. halys was switched from a mixed diet to a monotypic diet, allowing us to determine the detectability of the initial diet in a time series of ≤3 days after the diet switch. We detected 68 unique plant species from 54 genera in the diet of two stink bug species, with fewer genera found per sample and a smaller diet breadth for P. rufipes than for H. halys. Both stink bug species generally prefer deciduous trees over gymnosperms and herbaceous plants. Landscape type significantly impacted the observed genera in the diet of both stink bug species, whereas season only had a significant effect on the diet of H. halys.

CONCLUSION

This study provides further insights into the dietary composition of two polyphagous pentatomid pests and illustrates that metabarcoding can deliver a relevant species‐level resolution of host plant preference. © 2024 Society of Chemical Industry.
Intramolecular lactam cross‐linking of short oligoureas
Authors: Bachurska‐Szpala Paulina , Chojnacki Rafał , Pulka‐Ziach Karolina
Published: July 2024

Oligourea foldamers are known to fold into 2.5‐helices, stabilized by three‐centered hydrogen bonds, which makes them conformationally more rigid than peptides. Nevertheless, the folding propensity and conformational stability in solution depend on the length of the oligomer, as well as the temperature, solvent, and so forth. In the peptide field, there are many approaches known for constraining the backbone in the folded conformation, including the stapling of side chains by disulfide bridges, lactam formation, ring closing metathesis reaction, and others. In this work, we linked side chains by lactam bridges of short oligoureas (four residues), containing Glu‐ and Lys‐like residues. The designed oligoureas differed in the position of the Glu‐like residue. Next, the conformational properties of linear and cyclic compounds were studied in protic solvent (methanol) by nuclear magnetic resonance and circular dichroism. Importantly, it was discovered that larger macrocycles (24‐membered) are more tolerated with respect to the helical turn than smaller macrocycles (19‐membered) under the studied conditions.
Metolachlor Detection in Grain Using N‐Doped Carbon Quantum Dots and the Intramolecular Charge Transfer Effect
Authors: Wang Jinchen , Zhang Liyuan , Yu Runzhong
Published: July 2024

Herein, nitrogen is doped into carbon quantum dots (N‐CQDs) using a hydrothermal method for the rapid detection of metolachlor in grain. The morphological features, elemental compositions, and optical properties of the N‐CQDs are then analyzed and investigated using transmission electron microscopy, X‐ray photoelectron spectroscopy, and fluorescence spectroscopy, respectively. Based on the principle of intramolecular charge transfer, a fluorescent probe is constructed for the rapid detection of metolachlor. Under optimal experimental conditions, the fluorescence intensity change values of the N‐CQDs and metolachlor concentration have a good linear relationship when the concentration of metolachlor is in the range of 0.0125−2.5 μg mL−1. An evaluation of the method shows that the method has good selectivity, reproducibility, and stability, with a limit of detection of 1.63 μg kg−1 and a limit of quantification of 3.92 μg kg−1. The spiked recoveries of six real samples are tested using a spiked recovery assay that yielded spiked recoveries in the range of 105.05−87.13%, and their relative standard deviations (n = 3) ranged from 4.62% to 0.61%, indicating that the method can be used for detection in actual samples with good precision and stability.
Learning Model Based on Electrochemical Metallization Memristor with Cluster Residual Effect
Authors: Sun Quanhai , Chen Guanyu
Published: July 2024

Although a memristor model, subjected to electrochemical metallization mechanism, has been proposed based on the spontaneous decay of clusters in the previous work, it does not agree with the human forgetting accurately. Therefore, an improved model is meaningfully presented for the memristor with the cluster spontaneous decay by adding the residual effect. The former is due to the inward contraction of atoms driven by surface energy, while the latter is because of the balance of attractive and repulsive forces between atoms. The model fits well with the actual device. The forgetting is caused by the spontaneous decay. Memory retention is generated due to the added effect, which is also the internal cause of good agreement with the actual forgetting. Additionally, short‐term plasticity is converted to long‐term plasticity through the repeated learning. The efficiency of experiential learning using this model is much higher than that using the previous. It is shown that the physical mechanism of spontaneous decay in the cluster‐based channel is different from that in vacancy‐based or atom‐based channel. The model working under a non‐ideal condition with the temperature influence is discussed. Potential applications based on the model are stated.
Handling Partially Observed Trial Data After Treatment Withdrawal: Introducing Retrieved Dropout Reference‐Base Centred Multiple Imputation
Authors: Cro Suzie , Roger James H. , Carpenter James R.
Published: July 2024

The ICH E9(R1) Addendum (International Council for Harmonization 2019) suggests treatment‐policy as one of several strategies for addressing intercurrent events such as treatment withdrawal when defining an estimand. This strategy requires the monitoring of patients and collection of primary outcome data following termination of randomised treatment. However, when patients withdraw from a study early before completion this creates true missing data complicating the analysis. One possible way forward uses multiple imputation to replace the missing data based on a model for outcome on‐ and off‐treatment prior to study withdrawal, often referred to as retrieved dropout multiple imputation. This article introduces a novel approach to parameterising this imputation model so that those parameters which may be difficult to estimate have mildly informative Bayesian priors applied during the imputation stage. A core reference‐based model is combined with a retrieved dropout compliance model, using both on‐ and off‐treatment data, to form an extended model for the purposes of imputation. This alleviates the problem of specifying a complex set of analysis rules to accommodate situations where parameters which influence the estimated value are not estimable, or are poorly estimated leading to unrealistically large standard errors in the resulting analysis. We refer to this new approach as retrieved dropout reference‐base centred multiple imputation.
A functional data‐driven method for modeling degradation of waxy lubrication layer
Authors: Kang Wenda , Li Shixiang , Tian Yubin , Yin Ying , Sui Heliang , Wang Dianpeng
Published: July 2024

Wax is a prevalent lubrication material extensively employed in various engineering applications. Understanding the degradation characteristics of the waxy lubrication layer under diverse stress variables and levels is crucial for ensuring system security and reliability. Due to the unclear mechanism governing the degradation of the waxy lubrication layer under different stress variables, existing degradation models are unsuitable for modeling waxy lubrication layer degradation data. To address this challenge, we propose a functional data‐driven method leveraging dense observations of waxy degradation. Through extensive simulations and a case study, we demonstrate the superior performance and effectiveness of the proposed approach.
Macroinvertebrate response to run‐of‐river hydropower tailrace inflow: Spatial assessment of community and traits
Authors: Mihara Janine T. , Negishi Junjiro N. , Wu Junyi
Published: July 2024

Run‐of‐river (R‐O‐R) hydropower dams introduce two discontinuities in the river: the dam and the tailrace. Discontinuities can lead to changes in the water quality that may affect the survival of aquatic macroinvertebrates, depending on their traits. We investigated the invertebrate assemblage and community‐level traits in an urban river influenced by a small hydropower tailrace in Hokkaido, Japan. As a result of the tailrace inflow to the main channel, the bypassed reach was warmer, and the areas below the confluence were colder. Temperature was a consistent factor affecting the distribution of indicator taxa and of the five major taxa that contributed the most to dissimilarity, but other environmental factors also showed significant effects. At the community level, the weighted mean of taxa with warm preference showed a significant positive relationship with temperature, but taxa with cold preference did not appear to be filtered by the cold water delivered by the tailrace. However, sensitive taxa such as Ephemerella have already started showing negative responses to temperature. The observed distribution of cold‐preferring scrapers could negatively affect the energy transfer from primary producers to higher consumers in the bypassed reach. Appropriate mitigation of climate change effects in hydropower systems can be achieved by increasing the flow in the bypassed reach, especially during the summer months, to maintain a temperature regime that is adequate for the survival of macroinvertebrate populations and maintenance of ecosystem functions.