bluuebunny/crossref_metadata_2025 huggingface dataset:
3D Finite Element Models Reconstructed From 2D Dual‐Energy X‐Ray Absorptiometry (DXA) Images Improve Hip Fracture Prediction Compared to Areal BMD in Osteoporotic Fractures in Men (MrOS) Sweden Cohort
Authors: Grassi Lorenzo , Väänänen Sami P. , Jehpsson Lars , Ljunggren Östen , Rosengren Björn E. , Karlsson Magnus K. , Isaksson Hanna
Published: July 2023

Bone strength is an important contributor to fracture risk. Areal bone mineral density (aBMD) derived from dual‐energy X‐ray absorptiometry (DXA) is used as a surrogate for bone strength in fracture risk prediction tools. 3D finite element (FE) models predict bone strength better than aBMD, but their clinical use is limited by the need for 3D computed tomography and lack of automation. We have earlier developed a method to reconstruct the 3D hip anatomy from a 2D DXA image, followed by subject‐specific FE‐based prediction of proximal femoral strength. In the current study, we aim to evaluate the method's ability to predict incident hip fractures in a population‐based cohort (Osteoporotic Fractures in Men [MrOS] Sweden). We defined two subcohorts: (i) hip fracture cases and controls cohort: 120 men with a hip fracture (<10 years from baseline) and two controls to each hip fracture case, matched by age, height, and body mass index; and (ii) fallers cohort: 86 men who had fallen the year before their hip DXA scan was acquired, 15 of which sustained a hip fracture during the following 10 years. For each participant, we reconstructed the 3D hip anatomy and predicted proximal femoral strength in 10 sideways fall configurations using FE analysis. The FE‐predicted proximal femoral strength was a better predictor of incident hip fractures than aBMD for both hip fracture cases and controls (difference in area under the receiver operating characteristics curve, ΔAUROC = 0.06) and fallers (ΔAUROC = 0.22) cohorts. This is the first time that FE models outperformed aBMD in predicting incident hip fractures in a population‐based prospectively followed cohort based on 3D FE models obtained from a 2D DXA scan. Our approach has potential to notably improve the accuracy of fracture risk predictions in a clinically feasible manner (only one single DXA image is needed) and without additional costs compared to the current clinical approach. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).
Efficient removal of antibodies to adeno‐associated viruses by immunoadsorption
Authors: Boedecker‐Lips Simone , Judel Andreas , Holtz Stefan , Mayer Magnus , Klimpke Pascal , Kraus Daniel , Schreiner Thomas , Gerstmayer Bernhard , Eulitz Klaus , Mayer Magnus Christopher , Weinmann‐Menke Julia
Published: July 2023

Background

Gene therapies based on adeno‐associated viruses (AAV) are a therapeutic option to successfully treat monogenetic diseases. However, the influence of pre‐existing immunity to AAV can compromise the application of AAV gene therapy, most notably by the presence of neutralizing antibodies (NAb) to AAV.

Methods

In the following study, we investigated to what extent the treatment by immunoadsorption (IA) would reduce the levels of human anti‐AAV antibodies to AAV2 and AAV5. To that end, we screened blood sera from 40 patients receiving IA treatment because of underlying autoimmune disease or transplant rejection, with detectable AAV‐antibodies in 23 patients (22 by NAb detection, and 1 additionally by anti‐AAV5 ELISA analysis).

Results

Our results show that IA efficiently depleted anti‐AAV2 NAb with a mean reduction of 3.92 ± 1.09 log2 titer steps (93.4%) after three to five single IA treatments, 45% of seropositive subjects had an anti‐AAV2 titer below the threshold titer of 1:5 after the IA treatment series. Anti‐AAV5 NAb were reduced to below the threshold titer of 1:5 in all but one of five seropositive subjects. Analysis of total anti‐AAV5 antibodies by ELISA demonstrated an anti‐AAV5 antibody reduction over the IA treatment series of 2.67 ± 1.16 log2 titer steps (84.3%).

Conclusion

In summary, IA may represent a safe strategy to precondition patients with pre‐existing anti‐AAV antibodies to make this population eligible for an effective AAV‐based gene therapy.
Discriminatory episodes negatively impact the quality of life of Brazilian dental students: A cross‐sectional study
Authors: Sartori Letícia Regina Morello , Karam Sarah Arangurem , Chisini Luiz Alexandre , Corrêa de Oliveira Luísa Jardim , Aragão Sabóia Vicente de Paulo , Corrêa Marcos Britto
Published: July 2023

Purpose

This study aimed to evaluate whether discriminatory episodes occurring in the university environment were associated with dental students' self‐perceived overall quality of life and assess the cumulative effect of perceived discriminatory experiences on the overall quality of life.

Methods

In this cross‐sectional study, all students enrolled in three Brazilian dental schools were invited to participate in a survey between August and October 2019. The outcome was students’ self‐perceived quality of life, measured through the overall quality of life item of the World Health Organization—Quality of Life Abbreviated Version (WHOQOL‐BREF). Descriptive, bivariate, and multivariable logistic regression analyses (95% confidence intervals and α of 5%) were conducted using RStudio software.

Results

The sample was composed of 732 students (70.2% response rate). The great part was female (66.9%), white or yellow skin color (67.9%), and were children of highly educated mothers. About 68% of the students reported having experienced at least one of the seven discriminatory experiences presented in the questionnaire and 18.1% reported neutral or negative quality of life. In multivariable analyses, it was estimated that students who experienced at least one episode of discrimination were 2.54 times (95% CI: 1.47–4.34) more likely to report worse quality of life than their counterparts who reported no experience of discrimination. There was also a 25% (95% CI: 1.10–1.42) increase in the odds of reporting poorer quality of life for each additional discriminatory experience reported.

Conclusion

Reporting at least one discriminatory situation in the academic environment was associated with worse quality of life among dental students, and a cumulative effect was also noted.
Enterovirus 71 enters human brain microvascular endothelial cells through an ARF6‐mediated endocytic pathway
Authors: Zhu Yongzhe , Wang Xiaohang , He Zhiwei , Zhao Ping , Ren Hao , Qi Zhongtian
Published: July 2023

Infection of the central nervous system caused by enterovirus 71 (EV71) remains the main cause of death in hand‐foot‐and‐mouth disease. However, the mechanism responsible for how EV71 breaks through the blood‐brain barrier to infect brain cells has yet to be elucidated. By performing a high‐throughput small interfering RNA (siRNA) screening and validation, we found that the infection of human brain microvascular endothelial cells (HBMECs) by EV71 was independent of the endocytosis pathways mediated by caveolin, clathrin, and macropinocytosis but dependent on ADP‐ribosylation factor 6 (ARF6), a small guanosinetriphosphate (GTP)‐binding protein of the Ras superfamily. The specific siRNA targeting ARF6 markedly inhibited HBMECs susceptibility to EV71. EV71 infectivity was inhibited by NAV‐2729, a specific inhibitor of ARF6, in a dose‐dependent manner. The subcellular analysis demonstrated the co‐localization of the endocytosed EV71 and ARF6, while knockdown of ARF6 with siRNA remarkably influenced EV71 endocytosis. By immunoprecipitation assays, we found a direct interaction of ARF6 with EV71 viral protein. Furthermore, ARF1, another small GTP‐binding protein, was also found to participate in ARF6‐mediated EV71 endocytosis. Murine experiments demonstrated that NAV‐2729 significantly alleviated mortality caused by EV71 infection. Our study revealed a new pathway by which EV71 enters the HBMECs and provides new targets for drug development.
Job embeddedness and voluntary turnover in the face of job insecurity
Authors: Peltokorpi Vesa , Allen David G.
Published: July 2023

Two important contributions to the understanding of voluntary turnover are the ideas that employees become embedded in a net or web of restraining forces on‐ and off‐the‐job and that they experience varying degrees of control and desire that yield proximal withdrawal states explaining turnover motivations. We build on these ideas in two multi‐wave studies to study job insecurity, one of the most common work stressors and top concerns among employees around the world. Study 1 demonstrates that job search mediates the positive relationship between job insecurity and voluntary turnover, and that employees higher in on‐the‐job embeddedness are less likely to search for jobs despite job insecurity. Study 2 demonstrates that turnover intention mediates the positive relationship between job insecurity and voluntary turnover, and that employees higher in on‐the‐job embeddedness are less likely to contemplate quitting despite job insecurity. However, off‐the‐job embeddedness had opposite interactive effects, exacerbating the relationship of job insecurity with turnover.
Interpreting precipitation δ18O over eastern China for the Asian summer monsoon: Results from the last millennium simulations
Authors: Liu Yujia , Man Wenmin , Zhou Tianjun
Published: July 2023

The Asian summer monsoon (ASM) plays a major role in the Asian climate system, affecting nearly half of the world's population. The oxygen isotopes of speleothem calcite (δ18Oc) records in China provide important insights into past ASM changes; however, it remains controversial whether the δ18Oc records over eastern China (EC) mainly reflect the Indian summer monsoon (ISM) or East Asian summer monsoon (EASM). In this study, we estimate the relationships between precipitation‐weighted oxygen isotopes (δ18Opw) and various ASM indices over the last millennium based on the isotope‐enabled Community Earth System Model. The δ18Opw in EC mainly characterizes the intensity of the ISM and, to some extent, reflects the meridional wind component of the EASM, but it has an opposite relationship with the zonal wind component of the EASM. Although the limitations of various EASM definitions lead to the contrary relations between the δ18Opw and EASM indices, the δ18Opw in EC is accompanied by consistent EASM footprints. Moreover, although the meridional wind‐based EASM indices are negatively correlated with δ18Opw over EC, the relationships are much weaker than that with the ISM indices. The widespread negative δ18Opw signals extending from the Indian Peninsula to East Asia are closely coupled with the low‐level circulation over the ISM region. When considering the relationship between the EASM and δ18Opw over EC, the positive contribution from the Northwest Pacific offset the negative contribution from the remote Indian Ocean, leading to the insignificant correlation between the EASM indices and δ18Opw over EC.
Strengthening of Sri Lanka summer monsoon rainfall with rapid Arabian Sea warming
Authors: Kajakokulan Pathmarasa , Warnasooriya Anusha , Pathirana Gayan
Published: July 2023

Several studies have shown that rapid sea surface temperature (SST) warming in the tropical Indian Ocean (IO) significantly modulates the summer monsoon rainfall (SMR) over India. However, it remains unclear how the IO SST warming affects the SMR in Sri Lanka (SL). Therefore, based on observations and reanalysis data, this study investigates the impact of IO warming on SMR variability in the wet‐zone of SL during 2001–2020. The results revealed that the SMR (May–September) in SL's wet zone is increasing and is associated with rapid SST warming in the Arabian Sea during the summer monsoon. Although it is reported that the SMR may decrease over India due to the weakening of land‐sea thermal gradient in summer associated with IO warming, the rapid warming of the AS appears to enhance the SMR in the wet zone of SL. The warming of the AS during summer strengthened the low‐level easterlies, favouring moisture convergence and convection over SL, which enhanced the SMR of the wet zone of SL.
Adsorption of Congo red dye using metal oxide nano‐adsorbents: Past, present, and future perspective
Authors: Patil Yogita , Attarde Sanjay , Dhake Rajesh , Fegade Umesh , Alaghaz Abdel‐Nasser M. A.
Published: July 2023

The latest developments in the adsorption of organic dyes by adsorbents (metal oxides, modified metal oxides) were addressed in this review study. The main goal of this paper is to sort out the dispersion information of adsorbent materials, which are often employed in organic dye adsorption. The review dedicated to the specific dyes adsorption using various adsorbent (metal oxides, modified metal oxides). The review covers the adsorption process including parameters, kinetics, and isotherms. The review gives the brief information of Congo red (CR) adsorption using metal oxide nano‐adsorbents which provide readers with massive dye specific collection. For the first time, several metal‐doped materials that absorb organic dyes are summarized and addressed. The review includes adsorption of organic dyes using single metal oxide, bimetallic oxide, trimetallic oxide, and modified metal oxide. This study also summarized the effects of critical factors such as pH, initial dye concentration, adsorbent dosage, contact time, and temperature on dye adsorption utilizing metal oxide nano‐adsorbents. In addition, the kinetic and applied isotherm models have been discussed. Finally, a few recommendations are made for further research on adsorbent materials.
A new 532 nm, variable‐pulse‐structure, dual‐wavelength, KTP laser incorporating cryogen spray cooling, effectively treats rosacea
Authors: Bernstein Eric F.
Published: July 2023

Background

A new dual‐wavelength, high‐energy, solid‐state laser incorporating both 532 and 1064 nm wavelengths was developed with cryogen spray cooling and the unique ability to deliver three types of pulse structures including single pulses of a specific pulse‐duration or pulses composed of a train of subpulses in the millisecond or microsecond domain with an intervening delay over the selected pulse‐duration. We investigate the efficacy of this laser using all three pulse structures and the 532 nm wavelength for treating rosacea.

Methods

Twenty‐one subjects were enrolled in this IRB‐approved study. A total of up to three treatments were administered at monthly intervals. Each treatment consisted of a first pass tracing linear vessels with a 40 ms pulse‐duration immediately followed by a second pass using a 5 ms pulse, using all three available pulse structures. Assessment of cross‐polarized digital images by blinded physician observers compared baseline and 3‐month follow‐up images.

Results

Blinded observers correctly identified the posttreatment images 89% of the time, in 17 of 19 subjects completing the study, with an average overall improvement rating of 39% after only three treatments. Side effects were limited to short‐term erythema and edema.

Conclusion

This study demonstrates that this new, variable‐pulse‐structure, dual wavelength, solid state, KTP laser with dynamic cooling is a safe and effective for treating rosacea.
Does (customer data) size matter? Generating valuable customer insights with less customer relationship risk
Authors: Plangger Kirk , Marder Ben , Montecchi Matteo , Watson Richard , Pitt Leyland
Published: July 2023

Customer surveillance is a pervasive marketing practice that involves the collection, usage, and storage of customers' data from transactions, loyalty programs, and social media. Customer data are valuable to firms in gaining or maintaining an edge over competitors by developing superior customer insights that may assist product or service innovations. However, customer surveillance practices also risk customer relationships by potentially activating privacy and data security concerns. This article explores customer insight strategies that focus customer surveillance by assessing the insight value of data sources to avoid unnecessary data collection and capture. Three prediction experiments show that three distinct data source attributes, namely data quantity, data detail, and data content, are diagnostic of the prediction accuracy of customer psychographic characteristics and behavioral intentions. By demonstrating that customer insights are more (or less) valuable when derived from different data sources, this article shows that “more” data is not necessarily better. We advocate a smarter approach to customer surveillance practices that are selective in choosing to capture customer data that can yield more accurate customer insights while reducing the risk of jeopardizing customer relationships.
Coverage of radial forearm free flap donor site defect using another free flap
Authors: Lee Jong‐Koo , Lee Kyeong‐Tae
Published: July 2023

Background

Donor site defects following the radial forearm flap (RFF) harvest have been usually covered with skin grafting, which often lead to suboptimal outcomes and donor morbidities, including delayed healing and scar contractures. The present report aimed to evaluate the outcomes of using another free flap, the domino flap, for coverage of donor site defects following RFFF harvest.

Methods

Five patients (two males and three females) who underwent coverage of donor defects of RFFF using another free flap between 2019 and 2021 were reviewed. Their mean age was 74 years and the mean dimension of the defect of the RFF donor site was 8.7 × 5.6 cm. Four patients used an anterolateral thigh flap and one used a superficial circumflex iliac artery perforator flap.

Results

The mean size of the domino flaps were 12.2 × 5.8 cm. Distal stumps of radial vessels adopting retrograde flow were used as recipients in four cases, and proximal ones adopting anterograde in one. The donor site of the domino flaps was primarily closed. All patients recovered well without any postoperative complications. Aesthetically pleasing outcomes with no functional impairment related to scar contractures were observed in the donor site of RFF during the mean follow‐up of 15.7 months.

Conclusions

Use of another free flap for coverage of RFFF donor defects may provide rapid wound healing and satisfactory outcomes, and may be considered an alternative option in cases with large‐sized defects that are expected to take a long time to achieve complete healing with skin grafting.
The free Thenar flap for thumb pulp reconstruction: A case report
Authors: Faderani Ryan , Mann Ahdam , Kokkinos Constantinos , Nikkhah Dariush
Published: July 2023

The thumb is acknowledged to contribute significantly to hand function, accounting for up to 40% of its overall capability. Consequently, injuries affecting the thumb can have a profound impact on the quality of life experienced by patients. When it comes to the surgical reconstruction of thumb injuries, the primary objective is to promptly provide coverage of the affected area with glabrous skin, thus preserving both the length and functionality of the thumb. Managing injuries specifically involving the thumb pulp can be particularly challenging due to the digit's size and vital role. Acquiring an adequate amount of glabrous soft tissue poses a difficulty in such cases. Various reconstructive approaches, encompassing a range of options on the reconstructive ladder, have been documented for thumb pulp injuries. The most popular options include pedicled flaps and free flaps obtained from both the hands and feet. However, a consensus regarding the optimal method for reconstructing the thumb pulp has yet to be reached. We present a case of total thumb pulp reconstruction for a 40 × 30 mm defect using the free thenar flap in a 65‐year‐old carpenter who sustained a work‐related injury. This flap was designed and raised on the superficial branch of the radial artery with a single subcutaneous vein and a branch of the palmar cutaneous nerve, the flap measured 43 × 32 mm. It was inset transversely with an end‐to‐end arterial anastomosis to the ulnar digital artery, venous anastomosis to the dorsal digital vein and nerve coaptation to the ulnar digital nerve. The postoperative course was uneventful, and the patient was discharged the following day without any complications. Eight months after surgery, the patient was extremely satisfied with the results of the procedure in terms of both function and appearance. The patient had experienced an improvement in function, sensation, and aesthetics. The patient had a QuickDASH disability/symptom score of 15.91 and a QuickDASH work module score of 18.75; the range of motion in the treated thumb was almost the same as the opposite thumb. The patient successfully resumed work three weeks following the procedure, initially with modified duties, and fully regained their work capacity within six weeks. As the patient's primary concern was their ability to return to work, the utilization of a free thenar flap offered several distinct advantages. These included minimal post‐operative complications, facilitated by a single operative site, allowing for reconstruction under regional anesthesia. Moreover, the procedure was conducted in a single stage, enabling the patient to be discharged on the same day without the need for further procedures. Furthermore, similar to several other reconstructive options for the thumb, the utilization of a free thenar flap offered the advantage of providing high‐quality, like‐for‐like glabrous tissue.
Multiple digit resurfacing with a lateral thoracic free flap: Two‐stage mitten hand and division procedures
Authors: Ryoo Hyun Jung , Park Sang Hyun , Park Ji Ah. , Kim Youn Hwan , Shim Hyung‐Sup
Published: July 2023

Purpose

The conventional abdominal and groin flaps for resurfacing the defect have several disadvantages, including the risk of flap failure due to accidental traction or detachment, immobilization of the arm before division, and aesthetic dissatisfaction because of the flap bulkiness. The aim of this study was to share our experiences with the free lateral thoracic flap and elucidate the optimal timing of division in complex hand reconstruction, which yielded favorable outcomes in terms of both functionality and aesthetics.

Methods

This article is a retrospective review of multiple digit resurfacing using free tissue transfer from 2012 to 2022. Patients who underwent two‐stage operation including mitten hand creation using superthin thoracodorsal artery perforator (TDAp) free flap and secondary division were included. A flap was elevated over the superficial fascia layer the midportion between the anterior border of the latissimus dorsi and pectoralis major muscles and once the pedicle was found, an outline that matched the defect was created. A process named “pushing with pressure and cutting” was carried out before pedicle ligation until all the superficial fat tissue had been removed except for around the perforator. Two cases (18%) involved defects of the entire fingers reconstructed by TDAp flap with anterolateral thigh flap. Six cases (55%) had a super‐thin TDAp flap only. In two cases (18%), non‐vascularized iliac bone grafting was required for finger lengthening. One case (9%) was resurfaced with a TDAp chimeric flap including a skin paddle with the serratus anterior muscle. The primary outcome was defined as the survival or failure of the flap, while the secondary outcomes associated complications such as infection and partial flap necrosis. A statistical analysis was not performed due to the size of the case series.

Results

All 13 flaps survived completely without any complications. Flap dimension ranged from 12 cm × 7 cm to 30 cm × 15 cm. Mitten hand duration prior to division was 41.9 days on average which was essential for the optimal result. During the division procedures, there were nine cases of debulking (82%), six cases of split‐thickness skin graft (STSG) (55%), and three cases of Z‐plasty performed on the first web space (27%). The mean follow‐up period was 20.2 months. Mean Disability of the Arm, Shoulder, and Hand (DASH) Questionnaire score was 10.76.

Conclusions

We resurfaced severe soft tissue defects of multiple fingers with thin to super‐thin free flaps, mainly TDAp flaps. Surgeons can restore original hand shape using a two‐stage reconstructive strategy of mitten hand creation and proper division timing to create a 3‐dimensional hand structure, even in severely injured hands with multiple soft tissue defects of the digits.
Model‐based image updating in deep brain stimulation with assimilation of deep brain sparse data
Authors: Li Chen , Fan Xiaoyao , Aronson Joshua P. , Hong Jennifer , Khan Tahsin , Paulsen Keith D.
Published: July 2023

Background

Accuracy of electrode placement for deep brain stimulation (DBS) is critical to achieving desired surgical outcomes and impacts the efficacy of treating neurodegenerative diseases. Intraoperative brain shift degrades the accuracy of surgical navigation based on preoperative images.

Purpose

We extended a model‐based image updating scheme to address intraoperative brain shift in DBS surgery and improved its accuracy in deep brain.

Methods

We evaluated 10 patients, retrospectively, who underwent bilateral DBS surgery and classified them into groups of large and small deformation based on a 2 mm subsurface movement threshold and brain shift index of 5%. In each case, sparse brain deformation data were used to estimate whole brain displacements and deform preoperative CT (preCT) to generate updated CT (uCT). Accuracy of uCT was assessed using target registration errors (TREs) at the Anterior Commissure (AC), Posterior Commissure (PC), and four calcification points in the sub‐ventricular area by comparing their locations in uCT with their ground truth counterparts in postoperative CT (postCT).

Results

In the large deformation group, TREs were reduced from 2.5 mm in preCT to 1.2 mm in uCT (53% compensation); in the small deformation group, errors were reduced from 1.25 to 0.74 mm (41%). Average reduction of TREs at AC, PC and pineal gland were significant, statistically (p ⩽ 0.01).

Conclusions

With more rigorous validation of model results, this study confirms the feasibility of improving the accuracy of model‐based image updating in compensating for intraoperative brain shift during DBS procedures by assimilating deep brain sparse data.
DeepFittingNet: A deep neural network‐based approach for simplifying cardiac T1 and T2 estimation with improved robustness
Authors: Guo Rui , Si Dongyue , Fan Yingwei , Qian Xiaofeng , Zhang Haina , Ding Haiyan , Tang Xiaoying
Published: July 2023

Purpose

To develop and evaluate a deep neural network (DeepFittingNet) for T1/T2 estimation of the most commonly used cardiovascular MR mapping sequences to simplify data processing and improve robustness.

Theory and Methods

DeepFittingNet is a 1D neural network composed of a recurrent neural network (RNN) and a fully connected (FCNN) neural network, in which RNN adapts to the different number of input signals from various sequences and FCNN subsequently predicts A, B, and Tx of a three‐parameter model. DeepFittingNet was trained using Bloch‐equation simulations of MOLLI and saturation‐recovery single‐shot acquisition (SASHA) T1 mapping sequences, and T2‐prepared balanced SSFP (T2‐prep bSSFP) T2 mapping sequence, with reference values from the curve‐fitting method. Several imaging confounders were simulated to improve robustness. The trained DeepFittingNet was tested using phantom and in‐vivo signals, and compared to the curve‐fitting algorithm.

Results

In testing, DeepFittingNet performed T1/T2 estimation of four sequences with improved robustness in inversion‐recovery T1 estimation. The mean bias in phantom T1 and T2 between the curve‐fitting and DeepFittingNet was smaller than 30 and 1 ms, respectively. Excellent agreements between both methods was found in the left ventricle and septum T1/T2 with a mean bias <6 ms. There was no significant difference in the SD of both the left ventricle and septum T1/T2 between the two methods.

Conclusion

DeepFittingNet trained with simulations of MOLLI, SASHA, and T2‐prep bSSFP performed T1/T2 estimation tasks for all these most used sequences. Compared with the curve‐fitting algorithm, DeepFittingNet improved the robustness for inversion‐recovery T1 estimation and had comparable performance in terms of accuracy and precision.
BMI change during childhood, DNA methylation change at TXNIP, and glucose change during midlife
Authors: Ma Hao , Wang Xuan , Liang Zhaoxia , Li Xiang , Heianza Yoriko , He Jiang , Chen Wei , Bazzano Lydia , Qi Lu
Published: July 2023

Objective

This study investigated whether changes in DNA methylation (DNAm) at TXNIP are associated with glycemic changes and whether such an association differs with early‐life adiposity changes.

Methods

A total of 594 Bogalusa Heart Study participants who had blood DNAm measurements at two time points in midlife were included. Of them, 353 participants had at least four BMI measurements during childhood and adolescence. The incremental area under the curve was calculated as a measure of long‐term trends of BMI during childhood and adolescence.

Results

Increase in DNAm at TXNIP was significantly associated with decrease in fasting plasma glucose (FPG) independent of covariates (p < 0.001). The study found that the strength of this relationship was significantly modified by a trend of increasing BMI during childhood and adolescence (p‐interaction = 0.003). Each 1% increase in DNAm at TXNIP was associated with a 2.90‐ (0.77) mg/dL decrease in FPG among participants with the highest tertile of BMI incremental area under the curve and a 0.96‐ (0.38) mg/dL decrease among those with the middle tertile, whereas no association was observed among participants with the lowest tertile.

Conclusions

These results indicate that changes in blood DNAm at TXNIP are significantly associated with changes in FPG in midlife, and this association was modified by BMI trends during childhood and adolescence.
Association of central obesity with retinal neurodegeneration: Cross‐sectional and longitudinal evidence from two countries
Authors: Zhang Shiran , Zhu Zhuoting , Yuan Yixiong , Chen Yanping , Bulloch Gabriella , Huang Wenyong , He Mingguang , Wang Wei
Published: July 2023

Objective

This study aimed to evaluate the association of central obesity with retinal neurodegeneration.

Methods

Databases from the UK Biobank study and the Chinese Ocular Imaging Project (COIP) were included for cross‐sectional and longitudinal analyses, respectively. Retinal ganglion cell‐inner plexiform layer thickness (GCIPLT) measured by optical coherence tomography (OCT) was used as a retinal indicator of neurodegeneration. All subjects were divided into six obesity phenotypes according to BMI (normal, overweight, obesity) and waist to hip ratio (WHR; normal, high). Multivariable linear regression models were fitted to investigate the association of obesity phenotypes with GCIPLT.

Results

A total of 22,827 and 2082 individuals from UK Biobank (mean age: 55.06 [SD 8.27] years, women: 53.2%) and COIP (mean age: 63.02 [SD 8.35 years], women: 61.9%) were included, respectively. Cross‐sectional analysis showed GCIPLT was significantly thinner in normal BMI/high WHR individuals compared with normal BMI/normal WHR individuals (β = −0.33 μm, 95% CI = −0.61, −0.04, p = 0.045). But thinner GCIPLT was not observed in individuals with obesity/normal WHR. After 2‐year follow‐up in COIP, normal BMI/high WHR was associated with accelerated GCIPLT thinning (β = −0.28 μm/y, 95% CI = −0.45, −0.10, p = 0.02), whereas obesity/normal WHR was not.

Conclusions

Even with normal weight, central obesity was associated with accelerated GCIPLT thinning cross‐sectionally and longitudinally.
Investigating the impact of metabolic syndrome traits on telomere length: a Mendelian randomization study
Authors: Loh Nellie Y. , Rosoff Daniel , Noordam Raymond , Christodoulides Constantinos
Published: July 2023

Objective

Observational studies have reported bidirectional associations between metabolic syndrome (MetS) traits and short leukocyte telomere length (LTL), a TL marker in somatic tissues and a proposed risk factor for age‐related degenerative diseases. However, in Mendelian randomization studies, longer LTL has been paradoxically associated with higher MetS risk. This study investigated the hypothesis that shorter LTL might be a consequence of metabolic dysfunction.

Methods

This study undertook univariable and multivariable Mendelian randomization. As instrumental variables for MetS traits, all of the genome‐wide significant independent signals identified in genome‐wide association studies for anthropometric, glycemic, lipid, and blood pressure traits conducted in European individuals were used. Summary‐level data for LTL were obtained from a genome‐wide association study conducted in the UK Biobank.

Results

Higher BMI was associated with shorter LTL (β = −0.039, 95% CI: −0.058 to −0.020, p = 5 × 10−5) equivalent to 1.70 years of age‐related LTL change. In contrast, higher low‐density lipoprotein cholesterol was associated with longer LTL (β = 0.022, 95% CI: 0.007 to 0.037, p = 0.003) equivalent to 0.96 years of age‐related LTL change. Mechanistically, increased low‐grade systemic inflammation, as measured by circulating C‐reactive protein, and lower circulating linoleic acid levels might link higher BMI to shorter LTL.

Conclusions

Overweight and obesity might promote the development of aging‐related degenerative diseases by accelerating telomere shortening.
The future of energy harvesting: A brief review of MXenes‐based triboelectric nanogenerators
Authors: Mohan Raja , Ali Fathilah
Published: July 2023

Triboelectric nanogenerators (TENGs) have shown immense potential as self‐powering devices for energy harvesting, electronics, and self‐powered sensing devices. However, the performance of TENGs largely depends on the materials used, therefore, it is crucial to select appropriate materials. While dielectric polymers, metals, and inorganic materials have been commonly employed as active materials for TENGs, there is a need to explore new materials that offer improved performance. One promising material is two‐dimensional MXenes, which have shown exciting potential in various applications, including wearable sensors and electrochemical energy storage. For this reason, further research is needed to fully evaluate the performance of MXenes‐based TENGs and to determine their suitability for practical applications. This review emphasizes the significance of material selection in order to optimize the performance of triboelectric nanogenerators (TENGs). Here, the mechanism of TENGs is clearly explained for devices that convert mechanical energy into electric energy. The concept of the triboelectric effect is also described, which generates charge density on material surfaces, along with various types of TENG working modes. The selection of materials is thoroughly discussed, highlighting the growing interest in polymeric and biopolymeric materials, as well as functionalized and inorganic triboelectric materials. Also, exploration of materials that can enhance the output of TENGs, such as chemical modification techniques and the utilization of 2D materials like graphene and MXenes to improve triboelectricity is also included. The synthesis methods and techniques for MXenes are explored in detail. Furthermore, the performance of MXenes‐based TENGs for energy harvesting and self‐powered sensing is evaluated, and their potential applications in wearable devices are assessed. The study concludes by providing recommendations for future research on MXenes‐based TENGs and their applications in wearable devices.
Reevaluation of sodium thiosulfate otoprotection using the consensus International Society of Paediatric Oncology Ototoxicity Scale: A report from the Children's Oncology Group study ACCL0431
Authors: Orgel Etan , Knight Kristin R. , Villaluna Doojduen , Krailo Mark , Esbenshade Adam J. , Sung Lillian , Freyer David R.
Published: July 2023

In two randomized trials (Children's Oncology Group ACCL0431 and International Childhood Liver Tumour Strategy Group SIOPEL‐6), sodium thiosulfate (STS) demonstrated efficacy in preventing cisplatin‐induced hearing loss (CIHL). However, the measures used in those trials have been superseded by the consensus International Society of Paediatric Oncology (SIOP) Ototoxicity Scale. To provide benchmark data for STS efficacy when using this contemporary scale, we reanalyzed ACCL0431 hearing outcomes with the SIOP scale and using multiple timepoints. Compared to the control arm, STS significantly reduced CIHL when assessed by the SIOP scale across these different approaches. These results provide critical data to inform treatment discussions and support future potential trial designs comparing otoprotectants.
Biodegradable polymer‐based hydrogel as a bioactive carrier for dermatological cosmetics and pharmaceutical applications
Authors: Maijan Pattarawadee , Kongseng Piyawan , Bilhman Siwaporn , Dumjun Krittima , Wannaboworn Sirilak , Chantarak Sirinya , Voravuthikunchai Supayang P.
Published: July 2023

A novel biodegradable interpenetrating polymer network hydrogel impregnated with a plant extract was designed using a simple one‐pot free radical polymerization of polyacrylamide (PAM), poly(vinyl alcohol) (PVA) and gelatin (Gel). PAM/PVA/Gel hydrogels with different Gel contents (Gel‐0–Gel‐40) reached a maximum water absorbency of 1443%, which was approximately three times greater than PAM hydrogel. Biocompatibility assessment of all hydrogels on L929 fibroblast cells demonstrated no toxicity. Gel‐10 hydrogel with a water absorbency of 1120% presented the optimal tensile strength of 363 kPa. The compressive modulus of Gel‐10 hydrogel was 36.2 kPa with the ability to maintain shape under load. Gel‐10 hydrogel demonstrated a good adhesive property on various surfaces including paper, glass, aluminium and skin. A release study revealed a sustained release characteristic which involved Fickian diffusion. A plant extract,Quercus infectoria(Qi), was successfully impregnated as a bioactive agent into Gel‐10 hydrogel and demonstrated a broad spectrum of antibacterial activity against both Gram‐positive and Gram‐negative bacteria. In addition, theQi‐impregnated hydrogel possesses an excellent radical scavenging activity with 94.6% inhibition and antityrosinase activity with 88.4% inhibition. Studies on biodegradation in soil indicated that the external surfaces of Gel‐10 hydrogel were destroyed. The percentage weight loss of Gel‐10 hydrogel was 66.7%. Additionally, the water absorbency of Gel‐10 after a soil burial test was significantly decreased (421%), compared with 1120% before the test (P < 0.001). Gel‐10 hydrogel could be applied as a bioactive carrier in dermatological cosmetics and pharmaceutical products to prevent infections, deleterious effects from free radicals, and skin pigmentation disorders. © 2023 Society of Industrial Chemistry.
Registration of 12 soft red winter partial waxy wheat germplasms carrying one or two null alleles at the Wx loci
Authors: Ma Fengyun , Sturbaum Anne , Baik Byung‐Kee
Published: July 2023

Partial waxy wheat (Triticum aestivum L.) with reduced starch amylose content is potentially desirable for making bread with maintained moistness and extended shelf life and noodles with improved sensory acceptance. The USDA‐ARS developed and released 12 soft red winter (SRW) partial waxy wheat germplasms—SWQL‐K‐A‐1 (Reg. no. GP‐1077, PI 702623), SWQL‐K‐B‐1 (Reg. no. GP‐1080, PI 702626), SWQL‐K‐D‐1 (Reg. no. GP‐1082, PI 702628), SWQL‐K‐AB‐1 (Reg. no. GP‐1078, PI 702624), SWQL‐K‐AD‐1 (Reg. no. GP‐1079, PI 702625), SWQL‐K‐BD‐2 (Reg. no. GP‐1081, PI 702627), SWQL‐W‐A‐5 (Reg. no. GP‐1083, PI 702629), SWQL‐W‐B‐1 (Reg. no. GP‐1086, PI 702633), SWQL‐W‐D‐2 (Reg. no. GP‐1088, PI 702636), SWQL‐W‐AB‐4 (Reg. no. GP‐1084, PI 702630), SWQL‐W‐AD‐2 (Reg. no. GP‐1085, PI 702631), and SWQL‐W‐BD‐1 (Reg. no. GP‐1087, PI 702634)—by the introgression of one or two null alleles at the Wx loci from a soft spring waxy wheat germplasm to two SRW wheat cultivars. Twelve partial waxy wheat germplasms were selected from backcross‐four or backcross‐five derivatives of SRW wheat cultivars ‘Kristy’ and ‘Wilson’ (99ID490/5*Kristy and 99ID490/6*Wilson, respectively) by marker‐assisted selection. The kernel hardness of partial waxy wheat germplasms in Kristy and Wilson backgrounds ranged from 62.7 to 64.3 and from 28.4 to 31.7, respectively, whereas that of the corresponding wild type was 58.6 and 30.3, respectively. Amylose contents of isolated starches ranged from 23.9% to 25.8% in single‐null partial waxy wheat germplasms, from 18.4% to 24.3% in double‐null partial waxy wheat germplasms, and from 26.8% to 27.1% in parents and wild types. These partial waxy wheat germplasms would be useful for the development of SRW partial waxy wheat cultivars adapted to the eastern region of the United States and extending the use of SRW wheat in products that require a reduced starch amylose content.
Evidence‐based practice in physiotherapy in Argentina: Barriers, perceptions and behaviors
Authors: Bevacqua Nicolás , Intelangelo Leonardo
Published: July 2023

Background and Purpose

Evidence‐based practice (EBP) has been widely implemented in different areas of biomedical sciences. However, no precedents in Argentina have investigated the data regarding the knowledge and difficulties related to EBP in physiotherapists. The purpose was to describe the self‐reported behavior, knowledge, skills, opinion, and barriers related to the EBP of Argentinian physiotherapists.

Methods

A customized descriptive survey was conducted among 289 physical therapists in Argentina. The data were analyzed descriptively.

Results

The response rate was 56% (163/289). Argentinian physiotherapists update themselves through scientific articles, meetings, congresses, and courses. They reported having sufficient knowledge to use EBP, informing patients about treatment options, and considering their choices in the decision‐making process. However, there were inconsistencies in responses regarding experience with EBP during undergraduate or postgraduate studies. The most frequently reported barriers were lack of time, difficulty in understanding statistics, and difficulties with the English language of scientific articles.

Discussion

EBP in Argentine physiotherapists is still poorly understood. Time, language, and difficulties in understanding statistics are the most important barriers to the implementation of EBP. Undergraduate and postgraduate courses are warranted to improve the clinical decision‐making process.
Two residues determine nicotinic acetylcholine receptor requirement for RIC‐3
Authors: Noonan Jennifer D. , Beech Robin N.
Published: July 2023

Nicotinic acetylcholine receptors (N‐AChRs) mediate fast synaptic signaling and are members of the pentameric ligand‐gated ion channel (pLGIC) family. They rely on a network of accessory proteins in vivo for correct formation and transport to the cell surface. Resistance to cholinesterase 3 (RIC‐3) is an endoplasmic reticulum protein that physically interacts with nascent pLGIC subunits and promotes their oligomerization. It is not known why some N‐AChRs require RIC‐3 in heterologous expression systems, whereas others do not. Previously we reported that the ACR‐16 N‐AChR from the parasitic nematode Dracunculus medinensis does not require RIC‐3 in Xenopus laevis oocytes. This is unusual because all other nematode ACR‐16, like the closely related Ascaris suum ACR‐16, require RIC‐3. Their high sequence similarity limits the number of amino acids that may be responsible, and the goal of this study was to identify them. A series of chimeras and point mutations between A. suum and D. medinensis ACR‐16, followed by functional characterization with electrophysiology, identified two residues that account for a majority of the receptor requirement for RIC‐3. ACR‐16 with R/K159 in the cys‐loop and I504 in the C‐terminal tail did not require RIC‐3 for functional expression. Mutating either of these to R/K159E or I504T, residues found in other nematode ACR‐16, conferred a RIC‐3 requirement. Our results agree with previous studies showing that these regions interact and are involved in receptor synthesis. Although it is currently unclear what precise mechanism they regulate, these residues may be critical during specific subunit folding and/or assembly cascades that RIC‐3 may promote.
Global analysis of kinetics reveals the role of secondary nucleation in recombinant spider silk self‐assembly
Authors: Hovanová Veronika , Hovan Andrej , Žoldák Gabriel , Sedlák Erik , Humenik Martin
Published: July 2023

Recombinant spider silk proteins can be prepared in scalable fermentation processes and have been proven as sources of biomaterials for biomedical and technical applications. Nanofibrils, formed through the self‐assembly of these proteins, possess unique structural and mechanical properties, serving as fundamental building blocks for the fabrication of micro‐ and nanostructured scaffolds. Despite significant progress in utilizing nanofibrils‐based morphologies of recombinant spider silk proteins, a comprehensive understanding of the molecular mechanisms of nanofibrils self‐assembly remains a challenge. Here, a detailed kinetic study of nanofibril formation from a recombinant spider silk protein eADF4(C16) in dependence on the protein concentration, seeding, and temperature is provided. For the global fitting of kinetic data obtained during the fibril formation, we utilized the online platform AmyloFit. Evaluation of the data revealed that the self‐assembly mechanism of recombinant spider silk is dominated by secondary nucleation. Thermodynamic analyses show that both primary and secondary nucleations, as well as the elongation step of the eADF4(C16), are endothermic processes.
Application of physiologically based pharmacokinetic modeling to understand real‐world outcomes in patients receiving imatinib for chronic myeloid leukemia
Authors: Adattini Josephine A. , Adiwidjaja Jeffry , Gross Annette S. , McLachlan Andrew J.
Published: July 2023

We aimed to use physiologically based pharmacokinetic (PBPK) modeling and simulation to predict imatinib steady‐state plasma exposure in patients with chronic myeloid leukemia (CML) to investigate variability in outcomes. A validated imatinib PBPK model (Simcyp Simulator) was used to predict imatinib AUCss, Css,min and Css,max for patients with CML (n = 68) from a real‐world retrospective observational study. Differences in imatinib exposure were evaluated based on clinical outcomes, (a) Early Molecular Response (EMR) achievement and (b) occurrence of grade ≥3 adverse drug reactions (ADRs), using the Kruskal‐Wallis rank sum test. Sensitivity analyses explored the influence of patient characteristics and drug interactions on imatinib exposure. Simulated imatinib exposure was significantly higher in patients who achieved EMR compared to patients who did not (geometric mean AUC0‐24,ss 51.2 vs. 42.7 μg h mL−1, p < 0.05; Css,min 1.1 vs. 0.9 μg mL−1, p < 0.05; Css,max 3.4 vs. 2.8 μg mL−1, p < 0.05). Patients who experienced grade ≥3 ADRs had a significantly higher simulated imatinib exposure compared to patients who did not (AUC0‐24,ss 56.1 vs. 45.9 μg h mL−1, p < 0.05; Css,min 1.2 vs. 1.0 μg mL−1, p < 0.05; Css,max 3.7 vs. 3.0 μg mL−1, p < 0.05). Simulations identified a range of patient (sex, age, weight, abundance of hepatic CYP2C8 and CYP3A4, α1‐acid glycoprotein concentrations, liver and kidney function) and medication‐related factors (dose, concomitant CYP2C8 modulators) contributing to the inter‐individual variability in imatinib exposure. Relationships between imatinib plasma exposure, EMR achievement and ADRs support the rationale for therapeutic drug monitoring to guide imatinib dosing to achieve optimal outcomes in CML.