bluuebunny/crossref_metadata_2025 huggingface dataset:
Dynamic analysis and optimization of snatch lift based on barbell trajectory and on an anthropometric model comprised of six links
Authors: Jon Min Hyok , Rim Un‐Ryong
Published: November 2023

Weightlifting requires explosive strength, high speed, and flexibility. The aim of this research is to present a method based on barbell trajectory and on an anthropometric model comprised of six links for dynamic analysis and optimization of snatch lift. First, snatch lift is divided into nine stages based on barbell trajectory, velocity, and acceleration, while evaluating dynamic characteristics. Then, an anthropometric model of weightlifter which is comprised of six segments: shin, thigh, trunk, upper arm, forearm, and head is developed. Since the head accounts for more or less than 10% of body weight, it should be considered as one link of one degree of freedom. Physical properties such as mass and center of mass of each link are not given by statistical data, but by anthropometry and calculation in Solidworks program. Finally, for barbell trajectory as one of the most important performance indices in weightlifting, an optimal control problem is formulated to minimize a criterion function defined as the sum of work done by lifter during snatch lift and solved by using Pontryagin Maximum Principle (PMP). The proposed method is illustrated with case study, showing results in good agreement with ones by analysis of lifter's actual performances. It can help coach or weightlifter to improve the snatch technique.
Four stage CMOS operational amplifier, frequency compensated via active miller network
Authors: Attar Mahdis , Dehbovid Hadi , Ghorbani Alireza , Adarang Habib
Published: November 2023

A four‐stage CMOS operational amplifier is proposed in this work. The designed amplifier is frequency compensated via two differential blocks and two Miller capacitors. Unlike well‐known frequency compensation methods, the proposed compensation leaves the output node while exploiting extremely smaller capacitors compared to conventional approaches. The presented approach is modeled symbolically and realized at the circuit level via the Hspice circuit simulator and 0.18 μm CMOS technology. Good agreements between two separate simulation paths verify the validity and accuracy of the proposed approach. Ample simulation results are reported to investigate the proposed amplifier regarding parameter mismatches. According to the simulation results, the proposed four‐stage amplifier is an excellent candidate to be used in larger systems such as data converters, modulators, and sensors while it shows more than 169 dB as DC‐gain, 10 MHz as unity gain frequency with power consumption less than 500 μW.
Spatial and amplitude dynamics of neurostimulation: Insights from the acute intrahippocampal kainate seizure mouse model
Authors: Foutz Thomas J. , Rensing Nicholas , Han Lirong , Durand Dominique M. , Wong Michael
Published: November 2023

Objective

Neurostimulation is an emerging treatment for patients with drug‐resistant epilepsy, which is used to suppress, prevent, and terminate seizure activity. Unfortunately, after implantation and despite best clinical practice, most patients continue to have persistent seizures even after years of empirical optimization. The objective of this study is to determine optimal spatial and amplitude properties of neurostimulation in inhibiting epileptiform activity in an acute hippocampal seizure model.

Methods

We performed high‐throughput testing of high‐frequency focal brain stimulation in the acute intrahippocampal kainic acid mouse model of status epilepticus. We evaluated combinations of six anatomic targets and three stimulus amplitudes.

Results

We found that the spike‐suppressive effects of high‐frequency neurostimulation are highly dependent on the stimulation amplitude and location, with higher amplitude stimulation being significantly more effective. Epileptiform spiking activity was significantly reduced with ipsilateral 250 μA stimulation of the CA1 and CA3 hippocampal regions with 21.5% and 22.2% reductions, respectively. In contrast, we found that spiking frequency and amplitude significantly increased with stimulation of the ventral hippocampal commissure. We further found spatial differences with broader effects from CA1 versus CA3 stimulation.

Significance

These findings demonstrate that the effects of therapeutic neurostimulation in an acute hippocampal seizure model are highly dependent on the location of stimulation and stimulus amplitude. We provide a platform to optimize the anti‐seizure effects of neurostimulation, and demonstrate that an exploration of the large electrical parameter and location space can improve current modalities for treating epilepsy.

Plain Language Summary

In this study, we tested how electrical pulses in the brain can help control seizures in mice. We found that the electrode's placement and the stimulation amplitude had a large effect on outcomes. Some brain regions, notably nearby CA1 and CA3, responded positively with reduced seizure‐like activities, while others showed increased activity. These findings emphasize that choosing the right spot for the electrode and adjusting the strength of electrical pulses are both crucial when considering neurostimulation treatments for epilepsy.
“An act of compassion”: Emotion and the struggle for reproductive justice
Authors: Torres Julie
Published: November 2023

In dialogue with the rich scholarship on affect and the role of emotions in feminist knowledge production, this article explores how compassion is mobilized by activists in the struggle for reproductive justice. The author centers emotional knowledge by drawing on conversations with a reproductive justice advocate in central Florida, the musical anthem of Viva Ruíz and the Thank God for Abortion Collective, and her own personal experience with pregnancy loss. This includes a discussion of the ways that coloniality persists in the racialized and gendered landscape of reproductive politics, with particular attention to the experiences of Puerto Ricans. Ultimately, the article argues that an attunement to “a radical compassion”—that is, a deep concern and understanding of the intersectional oppressions that place value on certain bodies over others—engenders the possibilities of reproductive justice and produces alternative ways of knowing and feeling.
A “hard question”: Gender affirming care and gender distress in a social world
Authors: Martin Paula
Published: November 2023

Gender affirming care for youth is currently under political attack across the United States. Critics of affirming care often leverage a biological and fixed notion of gender as assigned at birth, which is at odds with how gender has been theorized academically for decades. Yet for some feminist clinicians, the popularized version of SOCIAL CONSTRUCTION present within rhetoric about the purpose of affirmative intervention also seems to undercut the legitimacy of care. In this article, I track how the difficult problems of the origins of gender itself, problems seemingly exposed by the invocation of the SOCIAL CONSTRUCTION of gender, are managed within the field of gender affirming care. I show how by drawing on the narrative power of very young gender expansive people, and by orienting clinical care away from identity towards DISTRESS, medical providers can align themselves both with feminist desires to change how gender ideology functions in the social world, and with the need to provide interventions that allow youth to embody the gender they desire.
Petroleum geology of conventional and unconventional resources: Introduction
Authors: Radwan Ahmed E. , Yin Shuai , Hakimi Mohammed Hail , Li Hu
Published: November 2023

Understanding reservoir, source, seal, migration pathways and trap characterization is the first step towards better energy resource exploitation. Several studies have been conducted in recent decades on the reservoir characteristics of conventional resources. Unconventional resources, on the other hand, have received more attention as alternative future energy solutions to depleted conventional resources. Drilling, exploration, development, and production of conventional and unconventional resources pose technical challenges to the energy industry. This special issue attempts to address the most pressing technical challenges in developing conventional reservoirs (such as sandstone and carbonate reservoirs) as well as unconventional energy sources (e.g., shale gas, shale oil, tight gas sand, coal bed methane, geothermal and gas hydrates). The special issue is composed of 21 papers that are classified into six different groups related to the physical and mechanical properties of reservoirs, petroleum geochemistry, petroleum geology, geological modelling, unconventional resource evaluation and conventional reservoir evaluation.
Semianalytical investigation on heat transfer in porous fins with temperature‐dependent thermal conductivity via the homotopy perturbation Sumudu transform approach
Authors: Gireesha B. J. , Pavithra C. G. , Keerthi M. L.
Published: November 2023

A unique investigation has been undertaken to analyze the heat transmission by convective and radiative mechanisms in a fully saturated penetrable fin of a longitudinal structure positioned on a leaning surface. This study introduces the fusion of the realms of Homotopy perturbation and Sumudu transform techniques to address a previously unexplored problem involving a moving fin with temperature‐dependent thermal conductivity. In prior research papers, the Homotopy Perturbation Sumudu Transform Method (HPSTM) was utilized to obtain analytical solutions for fins featuring temperature‐dependent thermal conductivity. However, in our current study, we employ the HPSTM to tackle a novel problem involving a moving porous fin. This fin exhibits temperature‐dependent thermal conductivity and is subjected to convection and radiation effects. Through a comparison with numerical results, the present study has validated the dependability of its findings. The dimensionless temperature profile has been investigated by studying its relationship with several parameters. Here we observed that when the Peclet number is augmented by 400%, there is a corresponding 1.11% increase in thermal outline at the fin's extremity. Enhancing the value of radiation parameter by 400% declines the temperature of the fin tip by 14.079%. This study encourages the application of the Homotopy perturbation Sumudu transform technique in more complex fin problems.
Umbilical cord prolapse in a sub‐Saharan setting: Incidence and perinatal mortality rate—A 4‐year retrospective review
Authors: Sium Abraham Fessehaye , Bekele Delayehu , Urgie Tadesse , Gebremedhin Genet , Gudu Wondimu , Fetene Awoke
Published: November 2023

Synopsis

Perinatal morality due to umbilical cord prolapse found in our study is comparable to that in high‐income settings.
Immunomodulatory effect of Myrtenol on benzo (a) pyrene‐induced lung cancer in Swiss albino mice via modulation of tumor markers, cytokines and inhibition of PCNA expression
Authors: Zhang Haoliang , Ramamoorthy Anuradha , Rengarajan Thamaraiselvan , Iyappan Petchi , Alahmadi Tahani A. , Wainwright Milton , Hussein‐Al‐Ali Samer Hasan
Published: November 2023

Lung cancer is one of the most common cancers in men. Although many diagnostic and treatment regimens have been followed in the treatment for lung cancer, increasing mortality rate due to lung cancer is depressing and hence requires alternative plant based therapeutics with with less side‐effects. Myrtenol exhibits anti‐inflammatory and antioxidant properties. Hence we intended to study the effect of Myrtenol on B(a)P‐induced lung cancer. Our study showed that B(a)P lowered hematological count, decreased phagocyte and avidity indices, nitroblue tetrazolium (NBT) reduction, levels of immunoglubulins, antioxidant levels, whereas Myrtenol treatment restored them back to normal levels. On the other hand, xenobiotic and liver dysfunction marker enzymes and pro‐inflammatory cytokines were elevated on B(a)P exposure, which retuned back to normal by Myrtenol. This study thus describes the immunomodulatory and antioxidant effects of Myrtenol on B[a]P‐induced immune destruction.
Edoxaban eliminates hypercoagulability evoked by transient temperature changes in human whole blood
Authors: Suzuki Anna , Hamada Satomi , Oono Ai , Hasegawa Yuki , Yamauchi Yasuteru , Okishige Kaoru , Hirao Kenzo , Sasano Tetsuo
Published: November 2023

Background

Thrombosis is a common critical complication relating to radiofrequency catheter ablation and cryoablation. There is a possibility that high‐temperature stimulation during radiofrequency ablation or low‐temperature stimulation during cryoablation may affect the coagulability of blood. In this study, we aimed to determine the impacts of transient temperature stimulations on the coagulability of whole blood and to clarify if edoxaban suppressed the hypercoagulability.

Methods

Citrated blood samples were drawn from 41 healthy subjects. Some blood samples were mixed with tissue factor (TF) and several concentrations of edoxaban (50, 100, and 200 ng/mL). Blood samples were exposed to several temperature stimulations for 1 min: heat stimulation (50°C) or cryostimulation (−20°C), and compared with control (37°C). Repeated cryostimulations or sequential cryo‐ and heat stimulation were also applied. Coagulability of whole blood was measured using a dielectric blood coagulometry. As an index of coagulability, the end of acceleration time (EAT) was used.

Results

Both heat‐ and cryostimulations significantly shortened the EAT compared to the control, indicating that hypercoagulability was induced by temperature stimulations. Application of TF enhanced and extended the hypercoagulability after the temperature stimulations. Sequential application of cryo‐ followed by heat stimulation further enhanced the hypercoagulability of blood. Application of edoxaban increased the EAT in a concentration‐dependent manner in control condition. Edoxaban at 100 or 200 ng/mL completely suppressed the shortening of EAT evoked by these temperature stimulations.

Conclusion

Transient temperature stimulations evoked hypercoagulability regardless of cryo‐ or heat stimulation. Edoxaban with 100 ng/mL or more eliminated this temperature‐stimulated hypercoagulability.
Recycling and transport of evapotranspiration over the Tibetan Plateau: Detected by a water vapour tracer method embedded in regional climate model
Authors: Tang Yingge , Dan Jingyu , Zhang Meng , Jiang Haojun , Gao Yanhong
Published: November 2023

With an average elevation of 4000 m, the Tibetan Plateau (TP) exerts a global influence on weather and climate. To investigate and quantify the impact of terrestrial evapotranspiration (ET) over the TP on both local and downstream regions, we employed the water vapour tracer (WVT) method integrated into the Weather Research and Forecasting (WRF) model to track the propagation of evaporative moisture across the TP. Based on precipitation landing location, termination of evaporative moisture over the TP was categorized into recycled ET (ETin, which precipitates inside the TP) and moving‐out ET (ETout, which precipitates outside the TP). Our findings reveal that ETin dominates 70% of ET moisture termination over the TP, exhibiting a decrease gradient from eastern to western regions. The majority of ETout spreads eastward with some reaching southward. Seasonal variations indicate that more than 75% of ET recycles during summer, while more ET moves out from TP in spring and autumn. The interplay between convection and advection leads to different reach‐outs for moving‐out ET in summer compared to other seasons: strong convection and diabatic heating plus a relative weak large‐scale advection result in shorter reach‐outs during summer, whereas weaker convection combined with strong advection leads to longer ‐reach‐outs in other seasons. This study enhances our understanding of terrestrial ET moisture transport over the TP as well as its mechanism influencing both local water cycle dynamics and downstream processes.
Influence of industrial blanching, cutting, and freezing treatments on in vitro gastrointestinal digestion stability of orange (Citrus sinensis L.) and lemon (Citrus limon L.) peel polyphenols
Authors: Ozdemirli Nurdan , Kamiloglu Senem
Published: November 2023

BACKGROUND

Citrus peels, which are often discarded as waste in the food‐processing industry, are rich sources of polyphenols. The aim of the current study was to investigate the influence of an industrial freezing process along with blanching and cutting pretreatments on the in vitro gastrointestinal digestion stability of orange (Citrus sinensis L.) and lemon (Citrus limon L.) peel polyphenols. The major polyphenols were identified and quantified with ultra‐performance liquid chromatography‐electrospray tandem mass spectrometry (UPLC‐ESI‐MS/MS) and high performance liquid chromatography‐photodiode array detector (HPLC‐PDA), respectively.

RESULTS

The results revealed that hesperidin and chlorogenic acid were the predominant flavonoid and phenolic acids in orange peels whereas, for lemon peels, eriocitrin and caffeic acid were the dominant flavonoid and phenolic acids, respectively. Blanching pretreatment enhanced the levels of major flavonoids in orange and lemon peels (by 39–82% and 54–146%, respectively) (P < 0.05) after in vitro gastrointestinal digestion. On the other hand, the application of cutting treatment after blanching significantly reduced the levels of flavonoids (23–62%) (P < 0.05); however, there was no statistically significant difference between the phenolic acid levels of cut and uncut citrus peels. Overall, the bioaccessibility of individual flavonoids and phenolic acids from frozen orange peels was generally slightly lower than that of untreated peels (9–34% and 9–49%, respectively). Nevertheless, frozen lemon peels contained higher bioaccessible flavonoids and phenolic acids in comparison with untreated peels (40–172% and 32–98%, respectively).

CONCLUSION

These results suggest that industrial freezing steps could largely preserve the bioaccessibility of polyphenols in orange and lemon peels. © 2023 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.
Repeat sentinel lymph node surgery for locally recurrent breast cancer after prior mastectomy
Authors: Schulze Amy K. , Hoskin Tanya L. , Mrdutt Mary M. , Mutter Robert W. , Hieken Tina J.
Published: November 2023

Background and Objectives

Current NCCN guidelines discourage repeat sentinel lymph node (SLN) surgery in patients with local recurrence (LR) of breast cancer following prior mastectomy. This study addresses the feasibility and therapeutic impact of this approach.

Methods

We identified 73 patients managed with repeat SLN surgery for post−mastectomy isolated LR. Lymphatic mapping was performed using radioisotope with or without lymphoscintigraphy and/or blue dye. Successful SLN surgery was defined as retrieval of ≥1 SLN.

Results

SLN surgery was successful in 65/73 (89%), identifying a median of 2 (range 1–4) SLNs, with 10/65 (15%) SLN‐positive. Among these, 5/10 (50%) proceeded to ALND. In unsuccessful cases, 1/8 (13%) proceeded to ALND. Seven of 10 SLN‐positive patients and 50/55 SLN‐negative patients received adjuvant radiotherapy. Chemotherapy was administered in 31 (42%) and endocrine therapy in 50 of 57 HR+ patients (88%). After 28 months median follow‐up, eight patients relapsed with the first site local in two, distant in five, and synchronous local/distant in one. No nodal recurrences were observed.

Conclusions

SLN surgery for patients with LR post−mastectomy is feasible and informative. This approach appears oncologically sound, decreases axillary dissection rates and may be used to tailor adjuvant radiation target volumes and systemic therapies.
Prenatal Diagnosis of Primrose Syndrome
Authors: Abdallah Wael , Spaggiari Emmanuel , Brisset Sophie , Dard Rodolphe , Attié Bitach Tania , Bault Jean Philippe , Quibel Thibault
Published: November 2023

Primrose syndrome is a very rare congenital malformation. Symptoms of this disorder may appear during childhood, but the diagnosis is identified in adulthood in the majority of cases. The prenatal diagnosis of Primrose syndrome is not developed in the literature. We present herein a case series of 3 cases with characteristic sonographic features. A dysmorphic metopic suture, downslanting palpebral fissures, a wide forehead, and agenesis of corpus callosum are the main signs. A missense mutation in ZBTB20 identified in whole exome sequencing can confirm the prenatal diagnosis of Primrose syndrome.
The Dubai Definition and Diagnostic Criteria of Laryngopharyngeal Reflux: The IFOS Consensus
Authors: Lechien Jerome R. , Vaezi Michael F. , Chan Walter W. , Allen Jacqueline E. , Karkos Petros D. , Saussez Sven , Altman Kenneth W. , Amin Milan R. , Ayad Tareck , Barillari Maria R. , Belafsky Peter C. , Blumin Joel H. , Johnston Nikki , Bobin Francois , Broadhurst Matthew , Ceccon Fabio P. , Calvo‐Henriquez Christian , Eun Young‐Gyu , Chiesa‐Estomba Carlos M. , Crevier‐Buchman Lise , Clarke John O. , Dapri Giovanni , Eckley Claudia A. , Finck Camille , Fisichella P. Marco , Hamdan Abdul‐Latif , Hans Stephane , Huet Kathy , Imamura Rui , Jobe Blair A. , Hoppo Toshitaka , Maron Lance P. , Muls Vinciane , O'Rourke Ashli K. , Perazzo Paulo S. , Postma Gregory , Prasad Vyas M.N. , Remacle Marc , Sant'Anna Geraldo D. , Sataloff Robert T. , Savarino Edoardo V. , Schindler Antonio , Siupsinskiene Nora , Tseng Ping‐Huei , Zalvan Craig H. , Zelenik Karol , Fraysse Bernard , Bock Jonathan M. , Akst Lee M. , Carroll Thomas L.
Published: November 2023

Objective

The objective of this work was to gather an international consensus group to propose a global definition and diagnostic approach of laryngopharyngeal reflux (LPR) to guide primary care and specialist physicians in the management of LPR.

Methods

Forty‐eight international experts (otolaryngologists, gastroenterologists, surgeons, and physiologists) were included in a modified Delphi process to revise 48 statements about definition, clinical presentation, and diagnostic approaches to LPR. Three voting rounds determined a consensus statement to be acceptable when 80% of experts agreed with a rating of at least 8/10. Votes were anonymous and the analyses of voting rounds were performed by an independent statistician.

Results

After the third round, 79.2% of statements (N = 38/48) were approved. LPR was defined as a disease of the upper aerodigestive tract resulting from the direct and/or indirect effects of gastroduodenal content reflux, inducing morphological and/or neurological changes in the upper aerodigestive tract. LPR is associated with recognized non‐specific laryngeal and extra‐laryngeal symptoms and signs that can be evaluated with validated patient‐reported outcome questionnaires and clinical instruments. The hypopharyngeal–esophageal multichannel intraluminal impedance–pH testing can suggest the diagnosis of LPR when there is >1 acid, weakly acid or nonacid hypopharyngeal reflux event in 24 h.

Conclusion

A global consensus definition for LPR is presented to improve detection and diagnosis of the disease for otolaryngologists, pulmonologists, gastroenterologists, surgeons, and primary care practitioners. The approved statements are offered to improve collaborative research by adopting common and validated diagnostic approaches to LPR.

Level of Evidence

5 Laryngoscope, 134:1614–1624, 2024
Patient Referral and Acceptance of Maxillomandibular Advancement for Obstructive Sleep Apnea
Authors: Rodin Julianna , Fiorella Michele , Crippen Meghan , Best Keisha , Taub Daniel , Champion Allen , Boon Maurits , Huntley Colin
Published: November 2023

Objective

Maxillomandibular advancement (MMA) is an effective surgical treatment for obstructive sleep apnea (OSA); however, it is unclear how many patients who are referred for MMA actually undergo surgery. This study aims to determine follow‐up rates for patients referred for MMA and the reasons behind their choices.

Methods

Via retrospective review, we assessed consecutive patients with OSA intolerant to continuous positive airway pressure (CPAP) who underwent drug induced sleep endoscopy (DISE) between 2018 and 2020 at our institution. Patients recommended for MMA based on DISE and other findings were included. Patients were then contacted and administered an IRB‐approved survey in present time.

Results

One hundred and fifty nine patients were referred to oral maxillofacial surgery (OMFS) for MMA consult. Seventy seven patients (48%) followed up with OMFS and 29 (18%) underwent MMA. Sixty two (40%) patients resumed CPAP. Fifty eight patients (36.5%) were lost to follow up.

Seventy three patients (46%) completed our survey. Of those patients, 37 (51%) followed up with OMFS and 17 (23%) underwent MMA. Patients who did not follow up with OMFS cited the invasiveness of the surgery (39%), recovery time (17%), or both (31%) as reasons. Those who pursued consultation cited inability to tolerate CPAP (73%), not being a candidate for inspire (14%), and desire to learn about alternative treatments (14%) as reasons. Of those who did not undergo MMA, 28.6% are not using OSA treatment.

Conclusion

Less than half of patients referred for MMA followed up, and less than half of those patients underwent MMA. Most patients cited concerns about the invasiveness of the surgery and recovery process.

Level of Evidence

4 Laryngoscope, 134:2964–2969, 2024
What is the impact of a multi‐component exercise intervention on the cure rate of urinary incontinence among older women living in the community?
Authors: Ricci Rachele , Avsar Pinar , Moore Zena , O'Connor Tom , Nugent Linda , Patton Declan
Published: November 2023

Aims

To determine the impact of a multi‐component exercise intervention on the cure rate of urinary incontinence (UI) among older women living in the community.

Method

A systematic search was conducted of five databases (Medline, Cumulative Index to Nursing and Allied Health Literature [CINAHL], Academic Search Complete, PubMed and Web of Science), grey literature and reference lists of relevant studies in December 2021– January 2022 and again between January 2023 and February 2023 when no additional new studies were identified. Key inclusion criteria were studies with female older adults above the age of 60, with any type of UI, residing in the community, addressing the effects of a multi‐component exercise intervention combining pelvic floor muscle training (PFMT), strength and balance exercises. The primary outcome of interest was the cure rate of UI in community‐dwelling older women (%).

Studies underwent quality appraisal using the RevMan Risk of Bias tool and the Evidence‐based Librarianship tool, identifying significant biases. A narrative synthesis presents results for all outcomes; a meta‐analysis was also performed for secondary outcomes.

Results

Following the PRISMA 2020 guidelines, a total of 596 records were identified from the systematic search. Five studies met the inclusion criteria. Participants receiving the intervention had a statistically significant mean cure rate of 44.0% (p < 0.05), which decreased at follow‐up, except for participants with stress UI. Participants receiving the intervention had significantly decreased frequency of UI episodes (p < 0.00001) and increased maximum walking speed (p < 0.0003) at a 3‐month follow‐up.

Conclusion

A multi‐component exercise, combining PFMT, strength and balance exercises, is effective in improving and curing UI, especially stress UI, in community‐dwelling older women.
Long‐Read Sequencing Resolves a Complex Structural Variant in PRKN Parkinson's Disease
Authors: Daida Kensuke , Funayama Manabu , Billingsley Kimberley J. , Malik Laksh , Miano‐Burkhardt Abigail , Leonard Hampton L. , Makarious Mary B. , Iwaki Hirotaka , Ding Jinhui , Gibbs J. Raphael , Ishiguro Mayu , Yoshino Hiroyo , Ogaki Kotaro , Oyama Genko , Nishioka Kenya , Nonaka Risa , Akamatsu Wado , Blauwendraat Cornelis , Hattori Nobutaka
Published: November 2023

Background

Parkin RBR E3 ubiquitin‐protein ligase (PRKN) mutations are the most common cause of young onset and autosomal recessive Parkinson's disease (PD). PRKN is located in FRA6E, which is one of the common fragile sites in the human genome, making this region prone to structural variants. However, complex structural variants such as inversions of PRKN are seldom reported, suggesting that there are potentially unrevealed complex pathogenic PRKN structural variants.

Objectives

To identify complex structural variants in PRKN using long‐read sequencing.

Methods

We investigated the genetic cause of monozygotic twins presenting with a young onset dystonia‐parkinsonism using targeted sequencing, whole exome sequencing, multiple ligation probe amplification, and long‐read sequencing. We assessed the presence and frequency of complex inversions overlapping PRKN using whole‐genome sequencing data of Accelerating Medicines Partnership Parkinson's disease (AMP‐PD) and United Kingdom (UK)‐Biobank datasets.

Results

Multiple ligation probe amplification identified a heterozygous exon three deletion in PRKN and long‐read sequencing identified a large novel inversion spanning over 7 Mb, including a large part of the coding DNA sequence of PRKN. We could diagnose the affected subjects as compound heterozygous carriers of PRKN. We analyzed whole genome sequencing data of 43,538 participants of the UK‐Biobank and 4941 participants of the AMP‐PD datasets. Nine inversions in the UK‐Biobank and two in AMP PD were identified and were considered potentially damaging and likely to affect PRKN expression.

Conclusions

This is the first report describing a large 7 Mb inversion involving breakpoints outside of PRKN. This study highlights the importance of using long‐read sequencing for structural variant analysis in unresolved young‐onset PD cases. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.
The effect of tube quality on externally calibrated quantitative nuclear magnetic resonance analysis: How bad can it be?
Authors: Ochoa Jessica L. , Germann Stephan , Conklin Breanna , Kurita Kenji , Russell David J. , Yang Cassie , Napolitano José G.
Published: November 2023

Externally calibrated quantitative nuclear magnetic resonance (NMR) approaches offer practical means to simultaneously evaluate chemical identity and content without the addition of calibrants to the test sample. Despite continuous advances in external calibration over the last few decades, adoption of these approaches has been slower than expected. Variations in NMR tube geometry are a commonly overlooked factor that can have a substantial effect on externally calibrated quantitation methods. In this report, we investigate the extent to which tube‐to‐tube volume variability can affect quantitative NMR outcomes. The results highlight the importance of considering tube quality during the development stages of externally calibrated quantitative methods. In addition, we propose a simple, yet effective volume correction strategy using the residual protonated solvent signal that, based on experiments with mixed NMR tubes of varying quality, alleviates the effect of tube‐to‐tube variability.
Deep learning‐assisted preclinical MR fingerprinting for sub‐millimeter T1 and T2 mapping of entire macaque brain
Authors: Gu Yuning , Pan Yongsheng , Fang Zhenghan , Ma Lei , Zhu Yuran , Androjna Charlie , Zhong Kai , Yu Xin , Shen Dinggang
Published: November 2023

Purpose

Preclinical MR fingerprinting (MRF) suffers from long acquisition time for organ‐level coverage due to demanding image resolution and limited undersampling capacity. This study aims to develop a deep learning‐assisted fast MRF framework for sub‐millimeter T1 and T2 mapping of entire macaque brain on a preclinical 9.4 T MR system.

Methods

Three dimensional MRF images were reconstructed by singular value decomposition (SVD) compressed reconstruction. T1 and T2 mapping for each axial slice exploited a self‐attention assisted residual U‐Net to suppress aliasing‐induced quantification errors, and the transmit‐field (B1+) measurements for robustness against B1+ inhomogeneity. Supervised network training used MRF images simulated via virtual parametric maps and a desired undersampling scheme. This strategy bypassed the difficulties of acquiring fully sampled preclinical MRF data to guide network training. The proposed fast MRF framework was tested on experimental data acquired from ex vivo and in vivo macaque brains.

Results

The trained network showed reasonable adaptability to experimental MRF images, enabling robust delineation of various T1 and T2 distributions in the brain tissues. Further, the proposed MRF framework outperformed several existing fast MRF methods in handling the aliasing artifacts and capturing detailed cerebral structures in the mapping results. Parametric mapping of entire macaque brain at nominal resolution of 0.35 0.35 1 mm3 can be realized via a 20‐min 3D MRF scan, which was sixfold faster than the baseline protocol.

Conclusion

Introducing deep learning to MRF framework paves the way for efficient organ‐level high‐resolution quantitative MRI in preclinical applications.
Sustained pain and macrophage infiltration in a mouse muscle contusion model
Authors: Cortez Ibdanelo , Gaffney Caitlyn M. , Crelli Caitlin V. , Lee Eric , Nichols James M. , Pham Hoang Vu , Mehdi Syed , Janjic Jelena M. , Shepherd Andrew J.
Published: November 2023

Introduction/Aims

Prior studies have emphasized the role of inflammation in the response to injury and muscle regeneration, but little emphasis has been placed on characterizing the relationship between innate inflammation, pain, and functional impairment. The aim of our study was to determine the contribution of innate immunity to prolonged pain following muscle contusion.

Methods

We developed a closed‐impact mouse model of muscle contusion and a macrophage‐targeted near‐infrared fluorescent nanoemulsion. Closed‐impact contusions were delivered to the lower left limb. Pain sensitivity, gait dysfunction, and inflammation were assessed in the days and weeks post‐contusion. Macrophage accumulation was imaged in vivo by injecting i.v. near‐infrared nanoemulsion.

Results

Despite hindpaw hypersensitivity persisting for several weeks, disruptions to gait and grip strength typically resolved within 10 days of injury. Using non‐invasive imaging and immunohistochemistry, we show that macrophage density peaks in and around the affected muscle 3 day post‐injury and quickly subsides. However, macrophage density in the ipsilateral sciatic nerve and dorsal root ganglia (DRG) increases more gradually and persists for at least 14 days.

Discussion

In this study, we demonstrate pain sensitivity is influenced by the degree of lower muscle contusion, without significant changes to gait and grip strength. This may be due to modulation of pain signaling by macrophage proliferation in the sciatic nerve, upstream from the site of injury. Our work suggests chronic pain developing from muscle contusion is driven by macrophage‐derived neuroinflammation in the peripheral nervous system.
Nonneurogenic female bladder outlet obstruction: Conservative and medical management
Authors: Perrin Andry , Corcos Jacques
Published: November 2023

Introduction

In nonneurogenic female bladder outlet obstruction (BOO), management goals include reduction of outlet resistance to increase urinary outflow and improve bladder voiding to prevent or reduce lower and upper urinary tract (LUT and UUT) function deterioration, by correcting the underlying etiology. As significant progress has been achieved in the conservative and pharmacological management of nonneurogenic female BOO, the purpose of this article is to review and summarize the current literature.

Materials and Methods

For this narrative review, a PubMed® search was performed by cross‐referencing the keywords “female bladder outlet obstruction,” “female voiding dysfunction,” “conservative management,” “pharmacological management,” and “treatment” with various terms related to the management of female BOO. Clinical practice guidelines and landmark reviews from the most renowned experts in the field were also used.

Management

This review discusses and summarizes the conservative and pharmacological management of nonneurogenic female BOO based on the most relevant data currently available in the literature.

Conclusion

The recent advances in the understanding of underlying mechanisms involved in female BOO allow for more individualized management. Conservative and pharmacological options show interesting outcomes, particularly in the context of a functional cause of BOO. Overall, the level of evidence is still low regarding the use of conservative and pharmacological measures and more long‐term data are required.
Actions matter more than words: From leader hypocrisy to employee withdrawal
Authors: Ilsev Arzu , Bayhan Karapinar Pinar , Metin Camgoz Selin
Published: November 2023

Leader hypocrisy refers to perceptions of a leader's word–deed misalignment. This study explores the mechanisms underlying the relationship between leader hypocrisy and psychological withdrawal as an indicator of nonprofit employees' disengagement from work. We propose that leader hypocrisy indirectly relates to employees' psychological withdrawal behaviors by influencing the quality of their relationships (leader‐member exchange [LMX]) with their leaders. Within this mechanism, we differentiate two routes that can lead followers' perceptions of leader hypocrisy to LMX: trust in the leader and negative emotions. Data were gathered from 182 employees working in a variety of nonprofit organizations (NPOs) in two waves. The findings support the indirect effect of leader hypocrisy on psychological withdrawal through trust in the leader and LMX. However, the mediating effect of negative emotions was not supported as the direct path from negative emotions to LMX was not significant. By adding a direct path, the alternative model demonstrated that when employees perceive their leader as a hypocrite, negative emotions can directly create psychological withdrawal rather than influencing withdrawal through impairing relationship quality perceptions.
Age‐related cognitive decline is accelerated in alcohol use disorder
Authors: Kurihara Kazuhiro , Shiroma Ayano , Koda Munenaga , Shinzato Hotaka , Takaesu Yoshikazu , Kondo Tsuyoshi
Published: November 2023

This study aimed to examine potential cognitive impairments in patients with alcohol use disorder (AUD), and explore the factors affecting them. We recruited 97 inpatients with AUD, showing superficially normal cognitive function (mini‐mental state examination score ≥24) for this study. We assessed cognitive function after a 4‐week post‐abstinence period using the Brief Assessment of Cognition in Schizophrenia‐Japanese version (BACS‐J). Relationships between BACS‐J subcategory/composite raw scores and Z‐scores (deviation from standard data in healthy Japanese) and background factors such as age, sex, education, smoking status, mini‐mental state examination score, body mass index, systolic blood pressure, severity of depression, alcohol consumption, and laboratory findings were analyzed. Multiple regression analysis showed that the age (p < 0.001) and total bilirubin level (p = 0.014) were worsening factors for the BACS‐J composite raw score, whereas education (p < 0.001) was a protective factor. An inverse correlation was apparent between the age and the composite Z‐score of the BACS‐J (r = −0.431, p < 0.001). Receiver operating characteristic (ROC) analysis identified 53 years as the cutoff age for predicting more than −2SD cognitive decline from the normal standard, with a high negative predictive value (95%). Patients with AUD aged ≥53 years showed more pronounced impairments in verbal memory, working memory, verbal fluency, and attention than those younger than 53 years (p < 0.05). These findings clearly demonstrate accelerated age‐related cognitive decline in patients with AUD, especially those aged ≥53 years, suggesting the necessity of early intervention in patients with AUD to prevent progressive cognitive impairment and preserve their quality of life.
Numerical approximation for hybrid‐dimensional flow and transport in fractured porous media
Authors: Zhao Jijing , Rui Hongxing
Published: November 2023

This article presents the stable miscible displacement problem in fractured porous media, and finite element discretization is constructed for this reduced model. The transmission interface conditions presented in this article enable us to derive a stability result and conduct the case where the pressure and concentration are both discontinuous across the fracture. The error estimates for and norm are established under the assumption of regular solutions. We perform some numerical examples to verify the theoretical analysis. Last, some unsteady physical experiments, more realistic test cases, are presented to prove the validity of the model and method.
Observational and genetic associations of adiposity with cardiopulmonary multimorbidity: Linear and nonlinear Mendelian randomization analysis
Authors: Song Zimin , Wang Wenxiu , Zhao Yimin , Xiao Wendi , Du Jie , Liu Zhonghua , Huang Tao , Tang Yida
Published: November 2023

Objective

Whether adiposity traits are causal risk factors for cardiopulmonary multimorbidity (CP‐MM) remains largely unknown. The aim of this study was to examine the causal role of adiposity traits in the development of CP‐MM.

Methods

This study involved 408,886 participants from the UK Biobank who had complete phenotypic and genetic data. Cox regression and Mendelian randomization (MR) analyses were conducted separately for observational and causal associations.

Results

During a median follow‐up of 8.7 years, 1492 incident CP‐MM were ascertained. In observational analysis, individuals with obesity had a hazard ratio (HR) of 1.51 (95% confidence intervals [CI]: 1.30–1.75) for developing CP‐MM, compared with those with normal body mass index (BMI). Restricted cubic spline analyses showed a U‐shaped relationship between continuous BMI and CP‐MM (p < 0.001), whereas WHRadjBMI exhibited a linear relationship (p = 0.828). Joint analysis revealed that maintaining ideal waist–hip ratio (WHR) in adults with overweight is still effective in preventing CP‐MM. In linear MR analysis, 1 kg/m2 increase in genetically predicted BMI and per 1% higher in genetically predicted WHRadjBMI was associated with 9% and 10% higher risk for incident CP‐MM, respectively. Nonlinear MR analyses demonstrated linearity between genetically predicted BMI or WHRadjBMI and CP‐MM.

Conclusions

Adiposity may play a causal role in CP‐MM development and represent a promising approach for multimorbidity prevention.
Bullous pemphigoid induced by IgG targeting type XVII collagen non‐NC16A/NC15A extracellular domains is driven by Fc gamma receptor‐ and complement‐mediated effector mechanisms and is ameliorated by neonatal Fc receptor blockade
Authors: Pigors Manuela , Patzelt Sabrina , Reichhelm Niklas , Dworschak Jenny , Khil'chenko Stanislav , Emtenani Shirin , Bieber Katja , Hofrichter Maxi , Kamaguchi Mayumi , Goletz Stephanie , Köhl Gabriele , Köhl Jörg , Komorowski Lars , Probst Christian , Vanderheyden Katrien , Balbino Bianca , Ludwig Ralf J , Verheesen Peter , Schmidt Enno
Published: November 2023

Bullous pemphigoid (BP) is an autoimmune blistering disease characterized by autoantibodies targeting type XVII collagen (Col17) with the noncollagenous 16A (NC16A) ectodomain representing the immunodominant site. The role of additional extracellular targets of Col17 outside NC16A has not been unequivocally demonstrated. In this study, we showed that Col17 ectodomain‐reactive patient sera depleted in NC16A IgG induced dermal–epidermal separation in a cryosection model indicating the pathogenic potential of anti‐Col17 non‐NC16A extracellular IgG. Moreover, injection of IgG targeting the murine Col17 NC14–1 domains (downstream of NC15A, the murine homologue of human NC16A) into C57BL/6J mice resulted in erythematous skin lesions and erosions. Clinical findings were accompanied by IgG/C3 deposits along the basement membrane and subepidermal blistering with inflammatory infiltrates. Disease development was significantly reduced in either Fc‐gamma receptor (FcγR)‐ or complement‐5a receptor‐1 (C5aR1)‐deficient mice. Inhibition of the neonatal FcR (FcRn), an atypical FcγR regulating IgG homeostasis, with the murine Fc fragment IgG2c‐ABDEG, a derivative of efgartigimod, reduced anti‐NC14–1 IgG levels, resulting in ameliorated skin inflammation compared with isotype‐treated controls. These data demonstrate that the pathogenic effects of IgG targeting the Col17 domain outside human NC16A/murine NC15A are partly attributable to antibody‐mediated FcγR‐ and C5aR1 effector mechanisms while pharmacological inhibition of the FcRn represents a promising treatment for BP. The mouse model of BP will be instrumental in further investigating the role of Col17 non‐NC16A/NC15A extracellular epitopes and validating new therapies for this disease. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.
Intrinsic low‐dielectric‐constant polyimides based on a novel diamine having −CF3 groups and kinkable 1,4‐diisopropylbenzene units
Authors: Nagella Sivagangi Reddy , Park Sung Soo , Chitumalla Ramesh Kumar , Jang Joonkyung , Ha Chang‐Sik
Published: November 2023

Polyimides (PIs) with low dielectric constants and optical transparency are of great interest in 5G/6G communication applications and in the microelectronics industry, where they are used as interlayer dielectric materials, wearable display devices and so forth. In this study, we designed and synthesized a novel fluorinated diamine called 4,4′‐(1,4‐phenylenebis(propane‐2,2‐diyl))diphenoxybis(2‐(trifluoromethyl)‐4‐aminobenzene) (BPBTAB) monomer from bisphenol‐P having diisopropyl benzene units and fabricated four novel BPBTAB‐X PIs. These PI films possess excellent properties such as a low dielectric constant (1.13–1.84 at 1 MHz), high 5% loss temperature (395–491 °C), moderate glass transition temperature (223–254 °C), good tensile modulus (0.827–1.076 GPa), excellent optical properties (T450 up to 83.37%), low moisture absorption (<0.63%) and good solubility in organic solvents. Hence, the as‐synthesized PI films exhibit excellent comprehensive properties for high‐frequency 5G/6G communication applications. © 2023 Society of Chemical Industry.
Analysis of small EV proteomes reveals unique functional protein networks regulated by VAP‐A
Authors: Barman Bahnisikha , Ramirez Marisol , Dawson Toni Renee , Liu Qi , Weaver Alissa M
Published: November 2023

Extracellular vesicles (EVs) influence cell phenotypes and functions via protein, nucleic acid, and lipid cargoes. EVs are heterogeneous, due to diverse biogenesis mechanisms that remain poorly understood. Our previous study revealed that the endoplasmic reticulum (ER) membrane contact site (MCS) linker protein vesicle associated protein associated protein A (VAP‐A) drives biogenesis of a subset of RNA‐enriched EVs. Here, we examine the protein content of VAP‐A‐regulated EVs. Using label‐free proteomics, we identified down‐ and upregulated proteins in small EVs (SEVs) purified from VAP‐A knockdown (KD) colon cancer cells. Gene set enrichment analysis (GSEA) of the data revealed protein classes that are differentially sorted to SEVs dependent on VAP‐A. Search Tool for the Retrieval of Reciprocity Genes (STRING) protein–protein interaction network analysis of the RNA‐binding protein (RBP) gene set identified several RNA functional machineries that are downregulated in VAP‐A KD SEVs, including ribosome, spliceosome, mRNA surveillance, and RNA transport proteins. We also observed downregulation of other functionally interacting protein networks, including cadherin‐binding, unfolded protein binding, and ATP‐dependent proteins.