bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of mirror therapy in the treatment of phantom limb pain in amputees: A systematic review of randomized placebo‐controlled trials does not find any evidence of efficacy
Authors: Guémann Matthieu , Olié Emilie , Raquin Lea , Courtet Philippe , Risch Nathan
Published: September 2022

Background and Objective

Phantom limb pain (PLP) concerns >50% of amputees and has a negative impact on their rehabilitation, mental health and quality of life. Mirror therapy (MT) is a promising strategy, but its effectiveness remains controversial. We performed a systematic review to: (i) evaluate the effectiveness of MT versus placebo in reducing PLP, and (ii) determine MT effect on disability and quality of life.

Databases and data treatment

We selected randomized‐controlled trials in five databases (Medline, Cochrane Library, CINAHL, PEDro and Embase) that included patients with unilateral lower or upper limb amputation and PLP and that compared the effects on PLP of MT versus a placebo technique. The primary outcome was PLP intensity changes and the secondary outcomes were PLP duration, frequency, patients' disability and quality of life.

Results

Among the five studies included, only one reported a significant difference between the MT group and control group, with a positive MT effect at week 4. Only one study assessed MT effect on disability and found a significant improvement in the MT group at week 10 and month 6.

Conclusions

Our systematic review did not allow concluding that MT reduces PLP and disability in amputees. This lack of strong evidence is probably due to (i) the low methodological quality of the included studies, and (ii) the lack of statistical power. Future trials should include a higher number of patients, increase the number and frequency of MT sessions, have a long‐term follow‐up and improve the methodological quality.

Significance

Recent meta‐analyses concluded that MT is effective for reducing phantom limb pain. Conversely, the present systematic review that included only studies with the best level of evidence did not find any evidence about its effectiveness for this condition. We identified many ways to improve future randomized‐controlled trials on this topic: increasing the number of participants, reducing the intra‐group heterogeneity, using a suitable placebo and intensifying the MT sessions and frequency.
Pain and masochistic behaviour: The role of descending modulation
Authors: Baudic Sophie , Poindessous‐Jazat Frédérique , Bouhassira Didier
Published: September 2022

Background

The mechanisms of pain perception in individuals with masochistic behaviour (MB) remain poorly documented. We hypothesized that MB is associated with context‐specific changes in descending pain modulation.

Methods

We compared the effects of four standardized sets of images with positive (erotic), negative (mutilations), masochistic or neutral emotional valences on the RIII nociceptive reflex evoked by electrical stimulation of the sural nerve and recorded on the ipsilateral biceps femoris in 15 controls and 15 men routinely engaging in MB. We systematically assessed the RIII reflex threshold and recruitment curves (up to the tolerance threshold), thermal (heat and cold) pain thresholds measured on the upper and lower limbs and responses to the pain sensitivity questionnaire, to compare basal pain perception between our two groups of participants. We also assessed anxiety, depression, empathy, alexithymia, high sensation seeking and catastrophizing, to investigate their potential influence on the emotional modulation of pain.

Results

Thermal pain thresholds, RIII reflex recruitment curves, and responses to the psychological and pain sensitivity questionnaires were similar in the two groups. Neutral, positive and negative images modulated the RIII reflex similarly in the two groups. By contrast, masochistic images induced a significant (p < 0.01) decrease in RIII reflex responses in subjects with MB, whereas it tended to increase these responses in control subjects.

Conclusions

Our data suggest that psychological profile, basal pain sensitivity and the emotional modulation of pain are normal in individuals with MB but that these subjects selectively engage descending pain inhibition in the masochistic context.

Significance

Decrease pain perception related to masochistic behaviours is associated with specific activation of descending pain inhibition.
Planning Challenges to Grid Reliability
Authors: DeCotis Paul A.
Published: September 2022

The Inflation Reduction Act (Act) passed by the United States Congress and signed into law by President Biden reaffirms the role of the United States as a world leader in advancing clean energy development and decarbonizing the US economy. The legislation contains $369 billion in funding for clean energy technology manufacturing, development, and use, and includes tax incentives for electrifying transportation. The Act itself is the largest climate and energy bill in US history. And the Act, together with the Bipartisan Infrastructure and Investment Jobs Act of 2021, represents the largest investment in industrial and manufacturing policy in US history. Energy policy support and financial incentives provided in the two pieces of legislation address: (1) energy affordability; (2) domestic energy supply diversity and security; (3) improved energy system efficiency, reliability, and resiliency; (4) decarbonization of the economy; and (5) expanded and enhanced environmental stewardship.
Complete skull of Bothriogenys fraasi (Mammalia, Artiodactyla, Anthracotheriidae) from the Early Oligocene, Fayum, Egypt
Authors: Sileem Afifi H. , Abu El‐Kheir Gebely A.
Published: September 2022

Bothriogenys is an endemic African anthracothere (Mammalia, Artiodactyla), which was first documented at the beginning of the last century by Schmidt in 1913. It is one of the most common genera and species that were unearthed from Early Oligocene deposits of North Africa, like those of the Fayum Depression, Egypt. It has been thought that the genus Bothriogenys probably give rise to the Early Miocene Brachyodus that dispersed to Europe and Asia around 20 million years ago. Here, we describe a complete skull of B. fraasi. The specimen is a nearly complete cranium with right canine, left and right upper first premolar‐upper third molar. The new skull has two mesial cristae on the upper premolars, three cristules on the metaconule and the upper fourth premolar has three roots. The main palatine foramina are located at the level of the mesial border of the upper fourth premolar and the internal choanae open well behind the upper molar. The cranial bones and the dentition indicate that Bothriogenys is located at the basal part of the subfamily Bothriodontinae and very close to early Miocene Brachyodus. If so Bothriogenys was likely among the first anthracotheriids to enter Africa. Continued anthracothere development and evolution ultimately gave rise to Early Miocene Brachyodus.
Remyelination in neuromyelitis optica spectrum disorder is promoted by edaravone through mTORC1 signaling activation
Authors: Luo Wenjing , Xu Huiming , Xu Li , Jiang Wei , Chen Chen , Chang Yanyu , Liu Chunxin , Tian Zhenming , Qiu Xiusheng , Xie Chichu , Li Xuejia , Chen Haijia , Lai Shuiqing , Wu Longjun , Cui Yaxiong , Tang Changyong , Qiu Wei
Published: September 2022

Neuromyelitis optica spectrum disorder (NMOSD) is a severe inflammatory autoimmune disease of the central nervous system that is manifested as secondary myelin loss. Oligodendrocyte progenitor cells (OPCs) are the principal source of myelinating oligodendrocytes (OLs) and are abundant in demyelinated regions of NMOSD patients, thus possibly representing a cellular target for pharmacological intervention. To explore the therapeutic compounds that enhance myelination due to endogenous OPCs, we screened the candidate drugs in mouse neural progenitor cell (NPC)‐derived OPCs. We identified drug edaravone, which is approved by the Food and Drug Administration (FDA), as a promoter of OPC differentiation into mature OLs. Edaravone enhanced remyelination in organotypic slice cultures and in mice, even when edaravone was administered following NMO‐IgG‐induced demyelination, and ameliorated motor impairment in a systemic mouse model of NMOSD. The results of mechanistic studies in NMO‐IgG‐treated mice and the biopsy samples of the brain tissues of NMOSD patients indicated that the mTORC1 signaling pathway was significantly inhibited, and edaravone promoted OPC maturation and remyelination by activating mTORC1 signaling. Furthermore, pharmacological activation of mTORC1 signaling significantly enhanced myelin regeneration in NMOSD. Thus, edaravone is a potential therapeutic agent that promotes lesion repair in NMOSD patients by enhancing OPC maturation.
Does providing free internet access to low‐income households affect COVID‐19 spread?
Authors: Goetz Daniel
Published: September 2022

This paper evaluates whether a policy of providing free, in‐home Internet for lower‐income households can reduce COVID‐19 case rates among those households. Using data from a pilot program in Toronto, we find that deploying free public WiFi in large apartment blocks within a low‐income neighborhood leads to a 14.4% reduction in weekly cases in that neighborhood. Having in‐home WiFi reduces the propensity of residents to visit businesses in the arts, entertainment, and recreation category, suggesting that WiFi benefits residents by providing in‐home substitutes for leisure activities.
c‐Rel–dependent Chk2 signaling regulates the DNA damage response limiting hepatocarcinogenesis
Authors: Leslie Jack , Hunter Jill E. , Collins Amy , Rushton Amelia , Russell Lauren G. , Ramon‐Gil Erik , Laszczewska Maja , McCain Misti , Zaki Marco Y. W. , Knox Amber , Seow Yixin , Sabater Laura , Geh Daniel , Perkins Neil D. , Reeves Helen L. , Tiniakos Dina , Mann Derek A. , Oakley Fiona
Published: September 2022

Background and Aims:

Hepatocellular carcinoma (HCC) is a leading cause of cancer‐related death. The NF‐κB transcription factor family subunit c‐Rel is typically protumorigenic; however, it has recently been reported as a tumor suppressor. Here, we investigated the role of c‐Rel in HCC.

Approach and Results:

Histological and transcriptional studies confirmed expression of c‐Rel in human patients with HCC, but low c‐Rel expression correlated with increased tumor cell proliferation and mutational burden and was associated with advanced disease. In vivo, global (Rel

−/−
) and epithelial specific (Rel

Alb
) c‐Rel knockout mice develop more tumors, with a higher proliferative rate and increased DNA damage, than wild‐type (WT) controls 30 weeks after N‐diethylnitrosamine injury. However, tumor burden was comparable when c‐Rel was deleted in hepatocytes once tumors were established, suggesting c‐Rel signaling is important for preventing HCC initiation after genotoxic injury, rather than for HCC progression. In vitro, Rel

−/−
hepatocytes were more susceptible to genotoxic injury than WT controls. ATM‐CHK2 DNA damage response pathway proteins were suppressed in Rel

−/−
hepatocytes following genotoxic injury, suggesting that c‐Rel is required for effective DNA repair. To determine if c‐Rel inhibition sensitizes cancer cells to chemotherapy, by preventing repair of chemotherapy‐induced DNA damage, thus increasing tumor cell death, we administered single or combination doxorubicin and IT‐603 (c‐Rel inhibitor) therapy in an orthotopic HCC model. Indeed, combination therapy was more efficacious than doxorubicin alone.

Conclusion:

Hepatocyte c‐Rel signaling limits genotoxic injury and subsequent HCC burden. Inhibiting c‐Rel as an adjuvant therapy increased the effectiveness of DNA damaging agents and reduced HCC growth.
Surgical Care Services in inaccessible zones: Targeted Palliative Care Accessibility Models for patients in resource‐limited settings
Authors: Shah Pritik A. , Tovani‐Palone Marcos Roberto
Published: September 2022

The coronavirus disease 2019 (COVID‐19) pandemic has caused a paradigm shift in the cancer care landscape, shifting from a palliative care approach to a need‐based approach. In these current and upcoming future times, patient‐ and community‐centred research becomes the cornerstone of collaborative assessment efforts for understanding and assessing Targeted Palliative Care (TPC) Accessibility Models for patients with oncological malignancies in resource‐limited settings. This short communication focuses on the models available for TPC for the continuation of care in oncological settings in resource‐limited geographic areas. Some programmes have used a Mixed Method Approach, highlighting their importance based on engagement volunteers and building trust and relationships in the community. Other studies have addressed the care system using a Rural Palliative Supportive Service Model for older adults living with life‐limiting chronic illness, showing that home‐based treatment for this population is feasible. Moreover, the Home Palliative Care Units (HPCU) model showed promising results in that patients cared for by HPCU had a fewer emergency visits and hospital admissions, in addition to being more likely to die at home with adequate palliation. During the ongoing pandemic, patients have experienced rapid clinical decline, requiring urgent conversations about their care wishes. They have been forced to make decisions on so‐called ‘Life and death’ issues. In this article we discuss the advantages, disadvantages, and possible changes implemented in the context of cancer surgical care in resource‐limited settings, in order to create a better assessment of geographic or demographic‐based, patient‐ and community‐centred TPC accessibility models for a more holistic development of cancer care programs.
Follow‐up the severity of abnormalities diagnosed in chest CT imaging of COVID‐19 patients: A cross‐sectional study
Authors: Honarmandpour Fatemeh , Jahangirimehr Azam , Tahmasbi Marziyeh , Khalighi Azam , Honarmandpour Azam
Published: September 2022

Background and Aims

This study aimed to evaluate the severity of diagnosed lung abnormalities of coronavirus disease 2019 (COVID‐19) patients based on the pre‐and postrecovery follow‐up chest computed tomography (CT) scan findings done at regular intervals.

Methods

This cross‐sectional study was performed in three phases. The severity of lung abnormalities was recorded and compared based on the initial and follow‐up chest CT findings carried out pre‐and at regular intervals (3 and 6 months) of postrecovery of COVID‐19 patients. Statistical data analysis was conducted using SPSS‐Version 26. Pearson Chi‐square test was used to analyze the results. p‐value < 0.05 was considered statistically significant.

Results

Regarding the initial chest CT findings, although ground‐glass opacity (GGO) was observed as the most common lung lesion, almost all the evaluated COVID‐19 patients had multiple lung lesions and involvements, especially with more involvement of the lower lobes. concerning the frequency of lung lesions and involvements in all phases of the study, almost no statistically significant differences were observed between male and female COVID‐19 patients and different age groups. However, older age groups had relatively more lung abnormalities due to Covid‐19 based on initial CT images which take more time to be eliminated. Lung abnormalities of Covid‐19 patients decreased significantly during the follow ups based on chest CT findings at different study phases.

Conclusion

According to evaluated pre‐ and post‐recovery chest CT scans, the frequency of lung lesions and lung involvement distribution decreased significantly in COVID‐19 patients, 3 and 6 months after recovery, and most of the recovered patients had no lung lesions or involvement anymore.
Fatigue performance investigation on the automotive welded structure under damped loads using the Taguchi method
Authors: Amarir Imane , Mounir Hamid , Rajad Omar , Amadane Yassine
Published: September 2022

In the present paper, a three‐dimensional numerical model has been built using ANSYS code to analyze the static and fatigue behavior of a welded design based on four rectangular profiles under damped loads for automotive application. The fatigue of the proposed design is generally influenced by a number of factors. The aim of this study is to investigate the effect of the load level, the stress ratio, the mean stress theory, the geometry size, the weld bead height, the temperature of the weld bead on the durability (P1), and the maximum of von Mises stress (P2) at the critical areas in the welded structure. As well as the length and the stiffness of the spring have been furtherly investigated. For this purpose, the application of the Taguchi method with computational simulation was performed for the target to determine the optimum operating parameters conditions. The results indicated that the optimum levels yielding a higher performance for P1 and P2 were (L1, L2, L2, L3, L1, L1, L3, and L3) and (L2, L3, L3, L3, L3, L3, L3, and L2), respectively. Thus, it revealed that the weld temperature was the predominant parameter influencing P1 and the mean stress theory factor was the most significant parameter influencing P2. This study led to defining a regression equation relating the output parameters with the selected factors. Consequently, the percentage error between regression equation calculations and computational outputs of fatigue life and maximum von Mises stress corresponding to the most optimal combinations obtained from Taguchi calculations was 0.92% and 0.63%, respectively. In fact, several parameters have been employed in this durability assessment to characterize the behavior of welded rectangular profiles prototype to predict the overall behavior of the suspension system of the automotive.
Uncertainty in high‐resolution hydrological projections: Partitioning the influence of climate models and natural climate variability
Authors: Moraga Jorge Sebastián , Peleg Nadav , Molnar Peter , Fatichi Simone , Burlando Paolo
Published: September 2022

A major challenge in assessing the impacts of climate change on hydrological processes lies in dealing with large degrees of uncertainty in the future climate projections. Part of the uncertainty is owed to the intrinsic randomness of climate phenomena, which is considered irreducible. Additionally, modelling the response of hydrological processes to the changing climate requires the use of a chain of numerical models, each of which contributes some degree of uncertainty to the final outputs. As a result, hydrological projections, despite the progressive increase in the accuracy of the models along the chain, still display high levels of uncertainty, especially at small temporal and spatial scales. In this work, we present a framework to quantify and partition the uncertainty of hydrological processes emerging from climate models and internal variability, across a broad range of scales. Using the example of two mountainous catchments in Switzerland, we produced high‐resolution ensembles of climate and hydrological data using a two‐dimensional weather generator (AWE‐GEN‐ 2d) and a distributed hydrological model (TOPKAPI‐ETH). We quantified the uncertainty in hydrological projections towards the end of the century through the estimation of the values of signal‐to‐noise ratios (STNR). We found small STNR absolute values (<1) in the projection of annual streamflow for most sub‐catchments in both study sites that are dominated by the large natural variability of precipitation (explains ~70% of total uncertainty). Furthermore, we investigated in detail specific hydrological components that are critical in the model chain. For example, snowmelt and liquid precipitation exhibit robust change signals, which translates into high STNR values for streamflow during warm seasons and at higher elevations, together with a larger contribution of climate model uncertainty. In contrast, projections of extreme high flows show low STNR values due to large internal climate variability across all elevations, which limits the potential for narrowing their estimation uncertainty.
Fabrication of macroporous apatite bone cements for non‐load bearing orthopedic applications
Authors: Dewangan Vimal Kumar , Sampath Kumar Trichirapalli Subramaniam , Doble Mukesh , Daniel Varghese Viju
Published: September 2022

Calcium deficient hydroxyapatite (CDHA)‐based apatite forming bone cements are well known for their bioactivity and bioresorbability. The formulation of CDHA‐based cements with improved macroporosity, injectability, and resorbability has been investigated. The solid phase consists of nanocrystalline hydroxyapatite (HA) and tricalcium phosphate (β‐TCP). The liquid phase is diluted acetic acid with disodium hydrogen phosphate as binding accelerator along with gelatin and chitosan to improve the injectability. A porogen agent either mannitol (as solid porogen) or polysorbate (as liquid porogen) is also used to improve the porosity. All combined in fine‐tuned composition results in optimal bone cements. The cement sets within the clinically preferred setting time (≤20 min) and injectability (>70%) and also stable at physiological pH (i.e., ~7.3–7.4). The XRD and FT‐IR analysis confirmed the formation of CDHA phase on day 7 when the after‐set cement immersed under phosphate buffer solution (PBS) at physiological conditions. The cements were found to have acceptable compressive strength for trabecular bone substitute. The cements were macroporous in nature with average pore size between 50 and 150 μm and were interconnected as confirmed by SEM, micro‐CT and MIP analysis. The prepared cements are degradable up to 22% and 19% in simulated body fluid and PBS respectively within 10 weeks of immersion at physiological conditions. The cements exhibit higher viability (%) (>110%) with L929 and MG63 cells compared to the control after 3 days of incubation. They also show increased proliferation, well spreading and extended filopodia with MG63 cells. Overall, the developed apatite forming bone cements seems to be suitable for low or non‐load bearing orthopedic applications.
Hydrogen sulfide attenuates uranium‐induced kidney cells pyroptosis via upregulation of PI3K/AKT/mTOR signaling
Authors: Hu Qiaoni , Zhang Rui , Zheng Jifang , Song Menghui , Gu Chaohao , Li Wanting
Published: September 2022

We have identified that hydrogen sulfide (H2S), a gaseous mediator, plays a crucial role in antioxidative, anti‐inflammatory, and cytoprotective effects on uranium (U)‐triggered rat nephrotoxicity. Pyroptosis is a special mode of inflammation and programmed cell death involved in the activation of inflammasome and Caspase‐1 and the release of inflammatory cytokines. This study aims to confirm whether H2S can alleviate U‐induced rat NRK‐52Ecell pyroptosis and to investigate the H2S underlying regulatory mechanism. Our results indicate that pretreatment with NaHS (an H2S donor) significantly inhibited U‐increased reactive oxygen species level, NLRP3, apoptosis‐related speck‐like protein consisting of a caspase recruitment domain (ASC), and cleaved Caspase‐1 proteins expression, gasdermin D messenger RNA (GSDMD mRNA) expression, interleukin (IL)−1β and IL‐18 contents, lactate dehydrogenase leakage, and numbers of double‐positive dying kidney cells. NaHS application evidently augmented phosphorylated PI3K, AKT, and mTOR expression as well as ratios of their respective phosphorylation to the corresponding total proteins which were downregulated by U treatment. But, LY294002 (a PI3K inhibitor) administration effectively abrogated the consequences of NaHS on the levels of p‐PI3K, cleaved Caspase‐1, ASC and NLRP3 proteins, GSDMD mRNA expression, and (IL)‐1β and IL‐18 contents. Simultaneously, LY294002 significantly reversed the effects of NaHS on U‐induced pyroptosis rate and cytotoxicity. Taken together, these results indicate that H2S ameliorated U‐triggered NRK‐52Ecells pyroptosis via upregulation of PI3K/AKT/mTOR pathway, suggesting a novel role for H2S in the management of nephrotoxicity caused by U exposure.
An immunogold single extracellular vesicular RNA and protein (AuSERP) biochip to predict responses to immunotherapy in non‐small cell lung cancer patients
Authors: Nguyen Luong T. H. , Zhang Jingjing , Rima Xilal Y. , Wang Xinyu , Kwak Kwang Joo , Okimoto Tamio , Amann Joseph , Yoon Min Jin , Shukuya Takehito , Chiang Chi‐Ling , Walters Nicole , Ma Yifan , Belcher Donald , Li Hong , Palmer Andre F. , Carbone David P. , Lee L. James , Reátegui Eduardo
Published: September 2022

Conventional PD‐L1 immunohistochemical tissue biopsies only predict 20%–40% of non‐small cell lung cancer (NSCLC) patients that will respond positively to anti‐PD‐1/PD‐L1 immunotherapy. Herein, we present an immunogold biochip to quantify single extracellular vesicular RNA and protein (AuSERP) as a non‐invasive alternative. With only 20 μl of purified serum, PD‐1/PD‐L1 proteins on the surface of extracellular vesicles (EVs) and EV PD‐1/PD‐L1 messenger RNA (mRNA) cargo were detected at a single‐vesicle resolution and exceeded the sensitivities of their bulk‐analysis conventional counterparts, ELISA and qRT‐PCR, by 1000 times. By testing a cohort of 27 non‐responding and 27 responding NSCLC patients, AuSERP indicated that the single‐EV mRNA biomarkers surpass the single‐EV protein biomarkers in predicting patient responses to immunotherapy. Dual single‐EV PD‐1/PD‐L1 mRNA detection differentiated responders from non‐responders with an accuracy of 72.2% and achieved an NSCLC diagnosis accuracy of 93.2%, suggesting the potential for AuSERP to provide enhanced immunotherapy predictions and cancer diagnoses within the clinical setting.
A multinational study of acute and long‐term outcomes of Type 1 galactosemia patients who carry the S135L (c.404C > T) variant of GALT
Authors: Katler Quinton S. , Stepien Karolina M. , Paull Nathan , Patel Sneh , Adams Michael , Balci Mehmet Cihan , Berry Gerard T. , Bosch Annet M. , DeLaO Angela , Demirbas Didem , Edman Julianna , Ficicioglu Can , Goff Melanie , Hacker Stephanie , Knerr Ina , Lancaster Kristen , Li Hong , Mendelsohn Bryce A. , Nichols Brandi , de Rezende Pinto Wladimir Bocca Vieira , Rocha Júlio César , Rubio‐Gozalbo M. Estela , Saad‐Naguib Michael , Scholl‐Buergi Sabine , Searcy Sarah , de Souza Paulo Victor Sgobbi , Wittenauer Angela , Fridovich‐Keil Judith L.
Published: September 2022

Patients with galactosemia who carry the S135L (c.404C > T) variant of galactose‐1‐P uridylyltransferase (GALT), documented to encode low‐level residual GALT activity, have been under‐represented in most prior studies of outcomes in Type 1 galactosemia. What is known about the acute and long‐term outcomes of these patients, therefore, is based on very limited data. Here, we present a study comparing acute and long‐term outcomes of 12 patients homozygous for S135L, 25 patients compound heterozygous for S135L, and 105 patients homozygous for two GALT‐null (G) alleles. This is the largest cohort of S135L patients characterized to date. Acute disease following milk exposure in the newborn period was common among patients in all 3 comparison groups in our study, as were long‐term complications in the domains of speech, cognition, and motor outcomes. In contrast, while at least 80% of both GALT‐null and S135L compound heterozygous girls and women showed evidence of an adverse ovarian outcome, prevalence was only 25% among S135L homozygotes. Further, all young women in this study with even one copy of S135L achieved spontaneous menarche; this is true for only about 33% of women with classic galactosemia. Overall, we observed that while most long‐term outcomes trended milder among groups of patients with even one copy of S135L, many individual patients, either homozygous or compound heterozygous for S135L, nonetheless experienced long‐term outcomes that were not mild. This was true despite detection by newborn screening and both early and life‐long dietary restriction of galactose. This information should empower more evidence‐based counseling for galactosemia patients with S135L.
Transcriptomic study in explanted liver from a patient with acute intermittent porphyria
Authors: To‐Figueras Jordi , Titos Esther , Aguilera Paula , Díaz Alba , Muñoz‐Luque Javier , Madrigal Irene , Badenas Celia , Torra Mercè , Fondevila Constantino , Colmenero Jordi
Published: September 2022

Acute intermittent porphyria (AIP) is a rare disease caused by a deficiency of hydroxymethylbilane synthase (HMBS), the third enzyme of the heme‐synthesis pathway. Decreased enzymatic activity in the liver induces an overproduction of heme‐precursors and acute neurological attacks. We report a 36‐years‐old female with AIP with a long‐term history of severe, disabling, recurrent attacks, who underwent curative liver transplantation. Tissue samples from the explant were obtained for transcriptome analysis. Whole RNA was extracted and 16 gene‐transcripts were selected and investigated by quantitative polymerase chain reaction. These included nine genes encoding enzymes that consecutively catalyze heme‐synthesis and catabolism in the liver (ALAS1; ALAD; HMBS; UROS; UROD; CPOX; PPOX; FECH; HMOX1). Additionally, we studied genes related to inflammation (IL6; TNF) insulin signaling (PGC‐1α; IGF‐1; FOXO‐1) and tryptophan metabolism (TDO2; IDO). Transcripts of eight house‐keeping genes were co‐measured for normalization. All transcripts were also measured in five control samples from healthy living liver donors. The transcriptome of the controls showed important differences between the various genes, with the first two genes of the heme‐synthesis pathway, ALAS1 and ALAD showing strikingly high mRNA levels compared to the consecutive HMBS gene. Transcripts of several genes significantly differed in the AIP liver compared to controls. Transcripts of HMOX1 and UROS were increased in the AIP liver whereas transcripts of UROD; CPOX, PPOX, and TDO2 were decreased. ALAS1 expression was not increased, possibly due to hemin administered to the patient before transplantation. These results highlight several transcriptomic changes related to heme homeostasis in AIP.
Differential Adaptation of Biventricular Myocardial Kinetic Energy in Patients With Repaired Tetralogy of Fallot Assessed by MR Tissue Phase Mapping
Authors: Ke Shi‐Ying , Weng Ken‐Pen , Chang Meng‐Chu , Wu Ming‐Ting , Li Yi‐He , Chien Kuang‐Jen , Lin Chu‐Chuan , Hsieh Kai‐Sheng , Chang Ming‐Hua , Pan Jun‐Yen , Peng Hsu‐Hsia
Published: September 2022

Background

The myocardial kinetic energy (KE) and its association with pulmonary regurgitation (PR) have yet to be investigated in repaired tetralogy of Fallot (rTOF) patients.

Purpose

To evaluate the adaptation of myocardial KE in rTOF patients by tissue phase mapping (TPM).

Study Type

Prospective.

Population

A total of 49 rTOF patients (23 ± 5 years old; male = 32), 47 normal controls (22 ± 1 year old; male = 29).

Field Strength/Sequence

3‐T/2D dark‐blood three‐directional velocity‐encoded gradient‐echo sequence.

Assessment

Left and right ventricle (LV, RV) myocardial KE in radial (KEr), circumferential (KEø), longitudinal (KEz) directions. The proportions of KE in each direction to the sum of all KE (KErøz): %KEr, %KEø, %KEz. PR fraction.

Statistical Test

Student's t test, multivariable regression. Statistical significance: P < 0.05.

Results

In rTOF group, LV KEz remained normal in systole (P = 0.565) and diastole (P = 0.210), whereas diastolic LV %KEz (62% ± 14% vs. 72% ± 7%) and systolic LV %KEø (9% ± 6% vs. 20% ± 7%) were significantly decreased. The KEr and %KEr of both ventricles significantly increased in the rTOF group (RV in diastole: 6 ± 3 vs. 3 ± 1 μJ and 54% ± 13% vs. 27% ± 7%). The rTOF group exhibited significantly higher RV/LV ratios of %KEr (systole: 1.3 ± 0.3 vs. 1.0 ± 0.3) and %KEø (systole: 1.6 ± 0.8 vs. 1.0 ± 0.3) and significantly lower ratios of %KEz in systole (0.7 ± 0.2 vs. 1.0 ± 0.1) and diastole (0.5 ± 0.2 vs. 0.9 ± 0.1). In multivariable regression analysis, the RV peak systolic KErøz, RV systolic KEz, and LV diastolic %KEø were independently associated with PR fraction in the rTOF group (adjusted R2 = 0.479).

Data Conclusion

In rTOF patients, the adaptation of the KE proportion occurred earlier than that of the KE amplitude, and the biventricular balance of %KE was disrupted. PR may cause differential KE adaptation in RV and LV. TPM‐derived KE may be useful in investigation of myocardial adaptation in rTOF patients.

Evidence Level

2

Technical Efficacy

Stage 3
Convergence of Vilenkin–Fourier series in variable Hardy spaces
Authors: Weisz Ferenc
Published: September 2022

Let be a variable exponent function satisfying the log‐Hölder condition and . We introduce the variable Hardy and Hardy–Lorentz spaces and containing Vilenkin martingales. We prove that the partial sums of the Vilenkin–Fourier series converge to the original function in the ‐ and ‐norm if . We generalize this result for smaller as well. We show that the maximal operator of the Fejér means of the Vilenkin–Fourier series is bounded from to and from to if , and . This last condition is surprising because the corresponding results for Fourier series or Fourier transforms hold without this condition. This implies some norm and almost everywhere convergence results for the Fejér means of the Vilenkin–Fourier series.
Darboux curves on product time scales
Authors: Altay Suroğlu Gülden
Published: September 2022

In this study, we give the structure of ruled surfaces parameterized on a product time scale. Mean and Gaussian curvatures of these surfaces are constructed on distinct time scales. Then, we obtain principal curvatures for ruled surfaces. Finally, we will clarify the issue with some examples.
Extension of Q‐type spaces related with weight functions via convolution operators on Heisenberg groups
Authors: Shi Meimei , Dong Jianfeng , Li Pengtao
Published: September 2022

In this paper, in the setting of Heisenberg groups
, we introduce two classes of
‐type spaces related with weight functions denoted by
. We investigate several basic properties of
, including the average oscillation property, the John–Nirenberg‐type inequality and the relations with classical function spaces. By the family of convolution operators
, we extend
, to the function spaces on the Siegel upper half space
. The wavelet characterizations of
are also obtained.
Explicit decay rate for the Gini index in the repeated averaging model
Authors: Cao Fei
Published: September 2022

We investigate the repeated averaging model for money exchanges: two agents picked uniformly at random share half of their wealth to each other. It is intuitively convincing that a Dirac distribution of wealth (centered at the initial average wealth) will be the long time equilibrium for this dynamics. In other words, the Gini index should converge to zero. To better understand this dynamics, we investigate its limit as the number of agents goes to infinity by proving the so‐called propagation of chaos, which links the stochastic agent‐based dynamics to a (limiting) nonlinear partial differential equation (PDE). This deterministic description has a flavor of the classical Boltzmann equation arising from statistical mechanics of dilute gases. We prove its convergence towards its Dirac equilibrium distribution by showing that the associated Gini index of the wealth distribution converges to zero with an explicit rate.
Nanoparticle‐mediated transgene expression of insulin‐like growth factor 1 in the growth restricted guinea pig placenta increases placenta nutrient transporter expression and fetal glucose concentrations
Authors: Wilson Rebecca L. , Lampe Kristin , Gupta Mukesh K. , Duvall Craig L. , Jones Helen N.
Published: September 2022

Fetal growth restriction (FGR) significantly contributes to neonatal and perinatal morbidity and mortality. Currently, there are no effective treatment options for FGR during pregnancy. We have developed a nanoparticle gene therapy targeting the placenta to increase expression of human insulin‐like growth factor 1 (hIGF1) to correct fetal growth trajectories. Using the maternal nutrient restriction guinea pig model of FGR, an ultrasound‐guided, intraplacental injection of nonviral, polymer‐based hIGF1 nanoparticle containing plasmid with the hIGF1 gene and placenta‐specific Cyp19a1 promotor was administered at mid‐pregnancy. Sustained hIGF1 expression was confirmed in the placenta 5 days after treatment. Whilst increased hIGF1 did not change fetal weight, circulating fetal glucose concentration were 33%–67% higher. This was associated with increased expression of glucose and amino acid transporters in the placenta. Additionally, hIGF1 nanoparticle treatment increased the fetal capillary volume density in the placenta, and reduced interhaemal distance between maternal and fetal circulation. Overall, our findings, that trophoblast‐specific increased expression of hIGF1 results in changes to glucose transporter expression and increases fetal glucose concentrations within a short time period, highlights the translational potential this treatment could have in correcting impaired placental nutrient transport in human pregnancies complicated by FGR.
An investigation into the dependence of virtual observation point‐based specific absorption rate calculation complexity on number of channels
Authors: Orzada Stephan , Akash Safi , Fiedler Thomas M. , Kratzer Fabian J. , Ladd Mark E.
Published: September 2022

Purpose

This study aims to find a relation between the number of channels and the computational burden for specific absorption rate (SAR) calculation using virtual observation point‐based SAR compression.

Methods

Eleven different arrays of rectangular loops covering a cylinder of fixed size around the head of an anatomically correct voxel model were simulated. The resulting Q‐matrices were compressed with 2 different compression algorithms, with the overestimation fixed to a certain fraction of worst‐case SAR, median SAR, or minimum SAR. The latter 2 were calculated from 1e6 normalized random excitation vectors.

Results

The number of virtual observation points increased with the number of channels to the power of 2.3–3.7, depending on the compression algorithm when holding the relative error fixed. Together with the increase in the size of the Q‐matrices (and therefore the size of the virtual observation points), the total increase in computational burden with the number of channels was to the power of 4.3–5.7.

Conclusion

The computational cost emphasizes the need to use the best possible compression algorithms when moving to high channel counts.
Noninvasive assessment of renal dynamics and pH in a unilateral ureter obstruction model using DCE MR‐CEST urography
Authors: Stabinska Julia , Singh Aruna , Haney Nora M. , Li Yuguo , Sedaghat Farzad , Kates Max , McMahon Michael T.
Published: September 2022

Purpose

To assess the potential of DCE MR CEST urography for assessing renal function in mice with unilateral ureter obstruction (UUO) by simultaneous pH and renal uptake/clearance measurements following injection of iopamidol.

Methods

The right ureter of nine mice was obstructed via suture ligation. The animals were imaged at day 1, 2, and 3 post‐obstruction on an 11.7T MRI scanner. Ninety‐six sets of saturated CEST images at 4.3 and 5.5 ppm were collected. Renal pH values were obtained by calculating the signal ratio for these two frequencies and using a pH calibration curve. Renal time activity curves were measured as a percentage change in the post‐injection CEST signal at 4.3 ppm relative to the average pre‐injection signal.

Results

For the healthy mice, the time activity curves of both kidneys were nearly identical and displayed rapid excretion of contrast. For the UUO mice, the dynamic CEST curves for the obstructed kidneys displayed prolonged time to peak (TTP) values and delayed contrast excretion compared with the contralateral (CL) kidneys. Renal pH maps of the healthy animals showed similar acidic values for both kidneys (pH 6.65 ± 0.04 vs 6.67 ± 0.02), whereas in the obstructed kidneys there was a significant increase in pH values compared with the CL kidneys (pH 6.67 ± 0.08 vs 6.79 ± 0.11 in CL and UUO kidneys, respectively).

Conclusion

Our findings indicate that DCE‐MR‐CEST urography can detect changes in renal uptake/excretion and pH homeostasis and distinguish between obstructed and unobstructed kidney as early as 1 day after UUO.
Physiotherapists nearly always prescribe exercise for rotator cuff‐related shoulder pain; but why? A cross‐sectional international survey of physiotherapists
Authors: Powell Jared K. , Schram Ben , Lewis Jeremy , Hing Wayne
Published: September 2022

Background and Aims

This cross‐sectional international survey explored the beliefs of physiotherapists regarding the possible mechanisms of benefit of exercise for rotator cuff‐related shoulder pain (RCRSP). Clinical practice guidelines recommend physiotherapists use exercise as a primary treatment to help people with RCRSP, but the explanations provided to patients by physiotherapists regarding its mechanism of effect is unknown.

Materials and Methods

Registered physiotherapists were surveyed about ‘how and why’ they believe exercise provides a clinical benefit for people with RCRSP. Information was also gathered about commonly used exercise types and preferred diagnostic labels. The survey was designed and reported in concordance with Consensus‐Based Checklist for Reporting of Survey Studies guidelines.

Results

Four hundred and eighty physiotherapists from forty‐nine countries completed the survey. Psychosocial and biomedical mechanisms of exercise were evenly selected by participants. Improving muscle strength, muscle endurance, pain self‐efficacy and reducing kinesiophobia, and fear avoidance beliefs were the most common individual mechanisms thought to underpin exercise therapy for RCRSP. Rotator cuff‐related shoulder pain was the most commonly used diagnostic label.

Discussion and Conclusion

Physiotherapists hold beliefs regarding exercise mechanisms that is largely concordant with the current evidence base, which is commendable. Future research should consider the patients perspective and consider testing commonly selected mechanisms of exercise, such as shoulder muscle strength, pain self‐efficacy and kinesiophobia as possible mediators of recovery.
Low T3 syndrome is associated with peripheral neuropathy in patients with type 2 diabetes mellitus
Authors: He Weilei , Pang Chunyang , Chen Luowei , Zeng Yaying , Gao Lingfei , Huang Huanjie , Zhang Wanli , Wang Xun , Deng Binbin
Published: September 2022

Introduction/Aims

Diabetic peripheral neuropathy (DPN) is one of the most common chronic complications of diabetes mellitus. Diabetic patients often have thyroid dysfunction. The aim of this study was to investigate the association between low triiodothyronine (T3) syndrome and DPN in patients with type 2 diabetes mellitus (T2DM).

Methods

A retrospective review was performed of 928 patients with T2DM for whom data was available for clinical manifestations and nerve conduction studies (NCS), and of 134 non‐diabetic controls. The composite Z scores of conduction velocity and amplitude were calculated. Low T3 syndrome was defined as T3 levels below the lower limit of the reference interval.

Results

Among the patients with T2DM, 632 (68.1%) had DPN, and a larger proportion of these patients presented with low T3 syndrome than patients without DPN. After adjusting for potential confounders, low T3 syndrome was independently associated with the occurrence of DPN (odds ratio [OR] = 2.049, 95% confidence interval [CI] 1.319–3.181, p = .001) and the severity of DPN (OR = 1.597, 95% CI 1.030–2.476, p = .036). Adding the criterion of low T3 syndrome improved the prognostic performance of the traditional model (age + gender + diabetic duration + glycated hemoglobin [HbA1c]) for predicting DPN.

Discussion

Low T3 syndrome is associated with a higher risk and increased severity of DPN in patients with T2DM. These findings suggest that low T3 syndrome could be a predictor for risk stratification in patients with T2DM.
Convergence analysis of the fractional decomposition method with applications to time‐fractional biological population models
Authors: Obeidat Nazek A. , Bentil Daniel E.
Published: September 2022

In this study, we present convergence analysis along with an error estimate for time‐fractional biological population equation in terms of the Caputo derivative using a new technique called the fractional decomposition method (FDM). Further, we present exact solutions to four test problems of nonlinear time‐fractional biological population models to show the accuracy and efficiency of the FDM. This method based on constructing series solutions in a form of rapidly convergent series with easily computable components and without the need of linearization, discretization and perturbations. The results prove that the FDM is very effective and simple for solving fractional partial differential equations in multi‐dimensional spaces, special cases of which we have described in this paper.
Opsoclonus‐myoclonus syndrome associated with neuroblastoma: Insights into antitumor immunity
Authors: Du Hongmei , Cai Weisong
Published: September 2022

Opsoclonus‐myoclonus syndrome (OMS) is a rare neurological disorder. Half of these cases occur in children with neuroblastoma. Neuroblastoma patients with OMS usually have better oncological outcomes than those without OMS even after stratification by tumor stage and age, indicating that factors mediating OMS may also inhibit tumor cell proliferation. Although the mechanisms underlying OMS remain undefined, the cytokines and lymphocytes alterations in the cerebrospinal fluid support the concept that it is a pattern of neuroinflammation due to an autoimmune effect. The presence of lymphoid follicles consisting of follicular dendritic cells, CD20+B lymphocytes, CD3+T lymphocytes, and CD68+macrophages in the tumor microenvironment in OMS‐associated neuroblastoma support the autoimmune nature of this disorder. This review focuses on the clinical and genetic features of OMS‐associated neuroblastoma, and we update readers on immune features of neuroblastoma with or without OMS to gain insights into antitumor immunity as it relates to tumor biology and prognosis.
Sirolimus for management of GI bleeding in blue rubber bleb nevus syndrome: A case series
Authors: Duong Jennifer T. , Geddis Amy , Carlberg Katie , Rudzinski Erin , Len Mary , Zheng Hengqi B.
Published: September 2022

Blue rubber bleb nevus syndrome (BRBNS) commonly presents with anemia from bleeding gastrointestinal (GI) vascular malformations. Management is highly variable, as no consensus guidelines for medical treatment currently exist. Sirolimus has been used in BRBNS to decrease GI bleeding and seems well tolerated, though questions remain regarding dosing, duration of therapy, and adverse effects. Here, we report our single‐center experience of four pediatric patients with BRBNS who were successfully treated with sirolimus and review the existing literature regarding sirolimus for treatment of GI bleeding in BRBNS. Further prospective studies are needed to establish optimal dosage, drug monitoring, and duration.