bluuebunny/crossref_metadata_2025 huggingface dataset:
Outcome of infantile nephropathic cystinosis depends on early intervention, not genotype: A multicenter sibling cohort study
Authors: Veys Koenraad , Zadora Ward , Hohenfellner Katharina , Bockenhauer Detlef , Janssen Mirian C. H. , Niaudet Patrick , Servais Aude , Topaloglu Rezan , Besouw Martine , Novo Robert , Haffner Dieter , Kanzelmeyer Nele , Pape Lars , Wühl Elke , Harms Erik , Awan Atif , Sikora Przemyslaw , Ariceta Gema , van den Heuvel Bert , Levtchenko Elena
Published: September 2022

Infantile nephropathic cystinosis (INC) is an inheritable lysosomal storage disorder characterized by lysosomal cystine accumulation, progressive kidney disease, and multiple extrarenal complications (ERCs). Cysteamine postpones the onset of end‐stage kidney disease (ESKD) and reduces the incidence of ERCs; however, cysteamine is generally initiated upon establishment of the renal Fanconi syndrome (FS) and partial loss of kidney function, whereas data on long‐term effects of cysteamine administered from neonatal age are lacking. An international multicenter retrospective cohort study of siblings with INC was set up to investigate the outcome in relation to age at initiation of cysteamine versus CTNS genotype, with attention to patients treated with cysteamine from neonatal age. None of the siblings treated from neonatal age (n = 9; age 10 ± 6 years) had reached ESKD, while 22% of their index counterparts (n = 9; age 14 ± 5 years) had commenced renal replacement therapy. Siblings treated with cysteamine from the onset of symptoms at a younger age compared with their index counterparts, reached ESKD at a significant older age (13 ± 3 vs. 10 ± 3 years, p = 0.002). In contrast, no significant difference in ERCs was observed between sibling and index patients, independently from the age at initiation of cysteamine. The CTNS genotype had no impact on the overall outcome in this cohort. In INC, presymptomatic treatment with cysteamine results in a better renal outcome in comparison to treatment initiated from the onset of symptoms. This justifies including cystinosis into newborn screening programs.

Synopsis

In infantile nephropathic cystinosis, presymptomatic treatment with cysteamine improves the renal outcome which justifies the inclusion of cystinosis into newborn screening programs.
Animal models of compression spinal cord injury
Authors: Ridlen Reggie , McGrath Kristine , Gorrie Catherine A.
Published: September 2022

Compression spinal cord injuries are a common cause of morbidity in people who experience a spinal cord injury (SCI). Either as a by‐product of a traumatic injury or due to nontraumatic conditions such as cervical myelitis, compression injuries are growing in prevalence clinically and many attempts of animal replication have been described within the literature. These models, however, often focus on the traumatic side of injury or mimic short‐term injuries that are not representative of the majority of compression SCI. Of this, nontraumatic spinal cord injuries are severely understudied and have an increased prevalence in elderly populations, adults, and children. Therefore, there is a need to critically evaluate the current animal models of compression SCI and their suitability as a method for clinically relevant data that can help reduce morbidity and mortality of SCI. In this review, we reviewed the established and emerging methods of animal models of compression SCI. These models are the clip, balloon, solid spacer, expanding polymer, remote, weight drop, calibrated forceps, screw, and strap methods. These methods showed that there is a large reliance on the use of laminectomy to induce injury. Furthermore, the age range of many studies does not reflect the elderly and young populations that commonly suffer from compression injuries. It is therefore important to have techniques and methods that are able to minimize secondary effects of the surgeries, and are representative of the clinical cases seen so that treatments and interventions can be developed that are specific.
Summertime precipitation extremes and the influence of atmospheric flows on the western slopes of the southern Andes of Perú
Authors: Villalobos‐Puma Elver , Flores‐Rojas Jose Luis , Martinez‐Castro Daniel , Morales Annareli , Lavado‐Casimiro Waldo , Mosquera‐Vásquez Kobi , Silva Yamina
Published: September 2022

Although climatologically dry, the western slopes of the southern Andes of Peru (WSA) can experience precipitation extremes (PEs) during the summer (December–February) resulting in great economic and human losses. Generally, WSA has a positive upslope gradient in precipitation, meaning more rain falls at higher elevations, but observations have shown this gradient can become negative with higher rainfall near the coastal cities. In this study we analyse 2000–2019 regional atmospheric patterns associated with different upslope precipitation gradients and PEs in WSA using principal component analysis methods and surface station observations. Results show important changes in the atmospheric circulation patterns during the occurrence of PE events. A prevailing pattern of negative southerly wind anomalies and regional warming of the southeastern Pacific Ocean leads to significant increases in moisture along the coast of WSA. Eastern moisture flows associated with the presence of the Bolivian High are observed at upper levels of the atmosphere and transport water vapour from the Amazon to the western side of the Andes. Additionally, there is a blocking effect aloft in response to an intense gradient of geopotential height that attenuates the easterly circulations. These large‐scale mechanisms act to concentrate high precipitable water amounts and high levels of convective available potential energy in the troposphere which favours the vertical velocities essential to trigger PEs. These results increase our knowledge of the large‐scale characteristics of PEs to help with forecasting these impactful events and protecting the more than 1.8 million people living in WSA.
Periodontal risk score: Initiation and model validation for 6,762 teeth
Authors: Saleh Muhammad H. A. , Tattan Mustafa , Troiano Giuseppe , Dukka Himabindu , Ravidà Andrea , Levine Robert , Wang Hom‐Lay , Miller Preston D.
Published: September 2022

Background

Tooth‐level prognostic systems are valuable tools for treatment planning and risk assessment of periodontally involved teeth. Recently the Miller‒McEntire prognosis index was found to outperform comparable systems. However, it had some limitations. The present study aimed to develop and evaluate the prognostic performance of a modified version that addresses most limitations of the previous model called the periodontal risk score (PRS).

Methods

Data were retrieved retrospectively from patients who received surgical and non‐surgical periodontal treatment at a university setting. Data on medical history and smoking status at baseline and the last maintenance visit were collected. Both univariate and multivariate Cox proportional hazard regression models were used to analyze the prognostic capability for predicting tooth loss due to periodontitis (TLP) risk.

Results

A total of 6762 teeth (281 patients) were followed up for a mean period of 22.6 ± 6.34 (10–47.6y) years. The PRS was successfully able to stratify the risk of TLP at baseline when the three different classes of association were compared for anterior and/or posterior tooth loss. After controlling for maintenance, age, and sex, the index showed an excellent predictive capacity for TLP with a Harrell C‐index of 0.947.

Conclusions

The periodontal risk score (PRS) displayed excellent predictive capability for anterior as well as posterior tooth loss due to periodontitis. This system was able to predict long‐term tooth loss with a very high accuracy  in a population treated mainly by dental students and periodontics residents. The use of this/similar prognosis system is advisable as a means to establish tooth prognosis.
Influence of storage conditions on the quality of semi‐defatted chia (Salvia hispanica L.) flour
Authors: Guiotto Estefania N. , Nolasco Susana M. , Tomás Mabel C.
Published: September 2022

Background

This research evaluates the effects of storage conditions on the quality of the semi‐defatted chia (Salvia hispanica L.) flour (SDCF), a by‐product from chia seed oil by cold pressing extraction with high nutritional value. For this purpose, SDCF was packaged in different types of packaging materials such as polyethylene (PE), polypropylene (PP), metalized biaxially oriented polypropylene films (BOPP), and triple kraft (K) and stored at 4 ± 1 and 20 ± 2°C for 240 days. Moisture content, fatty acids composition by GC, tocopherol content by HPLC, total phenolic content (TPC), and 2,2‐diphenyl‐1‐picrylhydrazyl (DPPH) radical scavenging activity assays by spectrophotometry were determined. Oxidative stability was monitored by peroxide values (PV), induction time (Rancimat), and free fatty acids content (FFA).

Results

Moisture content was below 9% during storage, and the fatty acids profile was stable under different storage conditions. The TPC and DPPH radical scavenging activity, γ‐ and δ‐ tocopherol contents decreased significantly (p < 0.05) with storage time; PV were lower than 10 meq O2/Kg oil under the studied parameters and the oxidative stability showed the highest level at 4 ± 1°C. The FFA content was <2% at 4 ± 1°C, overpassing this level after 120 days at 20 ± 2°C. SDCF showed a low microbial activity, which could be due to tocopherols and phenolic compounds.

Conclusions

Temperature and storage time had a significant influence on the quality of SDCF being BOPP packaging at 4 ± 1°C is the most effective method for their preservation from deteriorative processes.
Neoadjuvant therapy for melanoma: A critical appraisal
Authors: McKinley Sophia K. , Brady Mary S.
Published: September 2022

The treatment of advanced melanoma has significantly changed since the development of targeted and immune therapy. To date, these agents have primarily been used in the adjuvant or metastatic setting. Given several theoretical advantages, there is increased interest in the use of these new therapeutics in the neoadjuvant setting. In this review, we detail the potential benefits and pitfalls of neoadjuvant therapy for melanoma, review the currently available data, and describe ongoing neoadjuvant trials.
The Sommerlad–Furlow Modified Palatoplasty Technique: Postoperative Complications and Implicating Factors
Authors: Sakran Karim Ahmed , Wu Min , Alkebsi Khaled , Mashrah Mubarak Ahmed , Al‐Rokhami Remsh Khaled , Wang Yan , Mohamed Abdo Ahmed , Elayah Sadam Ahmed , Al‐Sharani Hesham Mohammed , Huang Hanyao , Shi Bing
Published: September 2022

Objective

To explore the incidence of postoperative complications and investigate the impact of preselected factors on functional and quality of life outcomes following the Sommerlad–Furlow modified palatoplasty technique.

Study Design

Retrospective cohort.

Methods

A total of 429 patients with cleft palate, who received Sommerlad–Furlow modified technique between 2011–2017 were enrolled. The postoperative complications including oronasal fistula (ONF), velopharyngeal insufficiency (VPI), and inadequate quality of life (QOL) were collected. Data of preselected factors including gender, age at palatoplasty, cleft type, cleft width, palatal width, pharyngeal cavity depth, and operation duration were also collected.

Results

Among 429 patients, 40.1% were males whereas 59.9% were females. The mean age at palatoplasty was 1.23 ± 0.69 (0.42–4) years, and the average cleft width was 10.15 ± 2.95 (4–27) mm. The cleft types had recorded rates of about 6.8%, 69.5%, 17.7%, and 6.1% of Veau I, II, III, and IV, respectively. The overall incidence rates of ONF, VPI, and inadequate QOL were 2.3%, 19.4%, and 31.3%, respectively. In both the univariate and multivariate analyses, the cleft type was significantly implicated in ONF formation (p = 0.023 and 0.032, respectively) whereas the velopharyngeal function was impacted by the palatoplasty age (p ˂ 0.001). The receiver operating characteristic curve indicated that age of palatoplasty ≥1.3 years (area under the curve = 0.611, p = 0.002) was the cutoff value for predicting the incidence of VPI.

Conclusions

The Sommerlad–Furlow modified technique appears to have appropriate postoperative outcomes, even in the wide cleft palate. The older age at palatoplasty has a major impact on the overall postoperative outcomes.

Level of Evidence

4 Laryngoscope, 133:822–829, 2023
Optimizing Botox regimens in patients with adductor spasmodic dysphonia and essential tremor of voice: A 31‐year experience
Authors: Stone Amy , Powell Maria E. , Hamers Kaitlyn , Fletcher K. Charles , Francis David O. , Courey Mark S. , Netterville James L. , Garrett C. Gaelyn
Published: September 2022

Objective

The purpose of this study was to quantitatively compare the effectiveness of unilateral and bilateral botulinum toxin A (BTX‐A) injections for mitigating undesirable weak/breathy voice quality and dysphagia for patients with adductor spasmodic dysphonia and/or essential tremor of voice (ETV).

Methods

Data were collected from the medical records of 319 patients, yielding three treatment cohorts: patients who received an equal dose bilateral injection regimen (BL=) throughout their course of treatment at VUMC, patients who switched to a unilateral injection regimen (UL), and patients who switched to an unequal dose bilateral injection regimen (BL≠). Changes in length of improvement, duration of weak/breathy voice, and dysphagia severity were compared.

Results

The BL = treatment group reported the longest duration of improved voice. Shorter periods of improved voice were reported at baseline by patients who later switched to UL or BL ≠ injection regimens. Patients receiving UL injections reported significantly reduced weak/breathy voice and dysphagia. Patients receiving BL ≠ injections reported increased length of improved voice; however, dysphagia symptoms increased. Ninety‐two percent of patients with ETV switched to a UL regimen, with 61% of patients transitioning within the first three injections.

Conclusions

Patients with pronounced dysphagia and extended periods of weak/breathy voice may benefit from a UL injection approach to mitigate side effects from BTX‐A without sacrificing improved voice outcomes. For patients seeking to extend their length of improved voice, a BL ≠ injection regimen may be effective provided the adverse side effects from BTX‐A are minimal. Patients with ETV may benefit from a UL injection approach at the outset of their course of treatment with BTX‐A.

Level of evidence

III.
Biological influences on coastal muddy sediment structure following resuspension
Authors: Clemo William Cyrus , Giles Katelyn D. , Dorgan Kelly M.
Published: September 2022

Shallow coastal muddy sediments are important for global nutrient cycling and carbon storage and provide a habitat for diverse communities of organisms. Bottom shear stress from physical disturbances such as storms and hurricanes resuspend coastal muds, disrupting their cohesive structure. How biological vs. physical processes affect reconsolidation of physically disturbed natural muds, however, is poorly understood. We compare the recovery of sediment properties related to compaction and cohesion of muds following physical disturbance. We hypothesized that recovery of cohesion would take longer than compaction and that changes in surface and subsurface cohesion would occur on different timescales. We collected muddy sediment cores and resuspended the top 5 cm in the lab to simulate storm disturbance. At several timepoints following resuspension (1–30 d), we measured sediment properties providing metrics of compaction (sediment height, porosity, grain size distribution, sound speed) and of surface and subsurface cohesion (erodibility, fracture behavior, exopolymeric substances [EPS]). Compaction and cohesion increased rapidly over the first 1–2 d after resuspension and continued to slowly increase for 2 weeks. Between 2 and 4 weeks, however, subsurface cohesion increased and turbidity decreased, consistent with sediment restabilization. In contrast, subsurface compaction decreased and eroded mass increased, suggesting destabilization. We attribute this apparent destabilization to delayed activity of small‐bodied infauna. Surprisingly, EPS concentration did not explain cohesion changes. These results highlight the importance of including biological parameters when predicting the recovery of sediment structure following a physical disturbance. This work has implications for understanding coastal sediment transport dynamics in frequently disturbed sediments.
Viability assessment and transplantation of fatty liver grafts using end‐ischemic normothermic machine perfusion
Authors: Patrono Damiano , De Carlis Riccardo , Gambella Alessandro , Farnesi Francesca , Podestà Alice , Lauterio Andrea , Tandoi Francesco , De Carlis Luciano , Romagnoli Renato
Published: September 2022

End‐ischemic viability testing by normothermic machine perfusion (NMP) represents an effective strategy to recover liver grafts having initially been discarded for liver transplantation (LT). However, its results in the setting of significant (≥30%) macrovesicular steatosis (MaS) have not been specifically assessed. Prospectively maintained databases at two high‐volume LT centers in Northern Italy were searched to identify cases of end‐ischemic NMP performed to test the viability of livers with MaS ≥ 30% in the period from January 2019 to January 2022. A total of 14 cases were retrieved, representing 57.9% of NMP and 5.7% of all machine perfusion procedures. Of those patients, 10 (71%) received transplants. Two patients developed primary nonfunction (PNF) and required urgent re‐LT, and both were characterized by incomplete or suboptimal lactate clearance during NMP. PNF cases were also characterized by higher perfusate transaminases, lower hepatic artery and portal vein flows at 2 h, and a lack of glucose metabolism in one case. The remaining eight patients showed good liver function (Liver Graft Assessment Following Transplantation risk score, −1.9 [risk, 13.6%]; Early Allograft Failure Simplified Estimation score, −3.7 [risk, 2.6%]) and had a favorable postoperative course. Overall, NMP allowed successful transplantation of 57% of livers with moderate‐to‐severe MaS. Our findings suggest that prolonged observation (≥6 h) might be required for steatotic livers and that stable lactate clearance is a fundamental prerequisite for their use.
Increased Drug‐Loading Enhances the Activity of Ellipticine in Poly(N‐(2‐hydroxypropyl) Methacrylamide) PHPMA‐Based Polymeric Micelles in 2D and 3D Cancer Cell Models
Authors: Al‐Nakashli Russul Mamdooh , Cao Cheng , Raveendran Radhika , Lu Hongxu , Stenzel Martina H.
Published: September 2022

Polymeric micelles are widely used as multifunctional drug carriers of poorly water‐soluble drugs, but the role of drug loading content is often overlooked. The purpose of this study is to investigate the cellular uptake and penetration of polymeric micelles with different drug loading contents and their effects on biological activities. In this study, poly(N‐(2‐hydroxypropyl) methacrylamide‐co‐methacrylic acid)‐block‐poly methyl methacrylate P(HPMA‐co‐MAA)‐b‐PMMA micelles are used as a nanocarrier for the encapsulation of the potent anticancer agent ellipticine (EPT). The micelles are loaded with various amounts of EPT and the physicochemical characteristics such as particle size, morphology, and zeta potential of blank and EPT loaded nanoparticles are studied. Moreover, fluorescent lifetime studies confirm that hydrophobic EPT is indeed in the PMMA micelle core. In vitro cytotoxicity tests using the glioma cell line U87MG reveal lower IC50 values when the cells are incubated with micelle with high drug loading content. The higher toxicity in micelles with higher drug loading content is associated with higher cellular uptake, which is monitored using laser scanning confocal microscopy and flow cytometry. Moreover, higher activity of micelles with higher drug loading is also observed in U87MG multicellular tumor spheroids although the difference is not significant.
Guangsangon E triggers mitochondria dysfunction and mitophagy in triple‐negative breast cancer and leads to non‐apoptotic cell death
Authors: Shen Yuhang , Han Zhuo , Wang Luping , Liang Yan , Zhang Xiaoyong , Li Wei , Li Shouxin , Tian Jingkui , Han Haote
Published: September 2022

Guangsangon E (GSE) is a natural product separated from Morus alba L. It has been reported to treat lung cancer through autophagy. However, whether GSE is effective in repressing triple‐negative breast cancer (TNBC) cells is yet to be elucidated. In the present study, GSE inhibited cell growth of MDA‐MB‐231, MDA‐MB‐453, and MDA‐MB‐468 cells. Moreover, GSE induced mitochondrial dysfunction, including membrane potential loss, mitochondria fission, and reactive oxygen species accumulation, and finally led to mitophagy‐related non‐apoptotic cell death. In the xenograft tumor nude mice, GSE treatment significantly reduced the size and weight of MDA‐MB‐231 tumors. The tumor inhibition rates of GSE treatment were 49.68% (low‐dose) and 48.73% (high‐dose). In summary, GSE is a potential anticancer drug available for treating TNBC with apoptosis resistance.
Review: PD‐L1 as an emerging target in the treatment and prevention of keratinocytic skin cancer
Authors: Vaishampayan Prajakta , Curiel‐Lewandrowski Clara , Dickinson Sally E.
Published: September 2022

Recent advances in the understanding and targeting of immune checkpoints have led to great progress in immune therapies against many forms of cancer. While many types of immune checkpoints are currently targeted in the clinic, this review will focus on recent research implicating the programmed cell death protein 1/programmed death‐ligand 1 (PD‐1/PD‐L1) axis as an emerging focus for the treatment of keratinocytic tumors. PD‐L1 is of particular interest in nonmelanoma skin cancer (NMSC), as it is not only upregulated in these tumors but is stimulated by environmental ultraviolet exposure. This response may also make PD‐L1 an excellent target for photochemoprevention using topically applied small molecule inhibitors. Here, we summarize recent investigations on PD‐L1 expression and clinically relevant immune checkpoint inhibitor treatment in cutaneous squamous cell carcinoma, basal cell carcinoma, and head and neck squamous cell carcinoma, as well as small molecule agents targeting PD‐L1 that may be useful for clinical development aiming at treatment or prevention of NMSC.
Montreal Cognitive Assessment Predicts the Short‐Term Risk of Lewy Body Disease in Isolated REM Sleep Behavior Disorder with Reduced MIBG Scintigraphy
Authors: Miyamoto Masayuki , Miyamoto Tomoyuki
Published: September 2022

Background

Long‐term follow‐up of isolated rapid eye movement (REM) sleep behavior disorder (IRBD) patients reveals a high risk of α‐synucleinopathies.

Objective

We explored the early clinical predictive factors of phenoconversion from IRBD to Parkinson's disease (PD) or dementia with Lewy bodies (DLB).

Methods

We assessed baseline office‐based cognitive test scores (Montreal Cognitive Assessment [MoCA‐J], Mini‐Mental State Examination [MMSE], and Frontal Assessment Battery [FAB]), motor function, and olfactory function in 36 consecutive polysomnography (PSG)‐confirmed IRBD patients with reduced metaiodobenzylguanidine (MIBG) accumulation. PD or DLB was confirmed by medical chart review retrospectively.

Results

Of 36 IRBD patients, 19 (n = 19, 52.8%) with abnormal MoCA‐J score (< 26) had significantly lower scores in trail making B, phonetic verbal fluency sub‐items in the executive domain, and in delayed recall in the memory domain. In total, 12 (33.3%) patients developed PD or DLB; seven of 12 patients (58.3%) developed DLB at a mean follow‐up period of 6.8 years. In the normal MoCA‐J group (n = 17, 47.2%), two patients developed PD, but none developed dementia. Furthermore, in the abnormal MoCA‐J group, seven patients developed DLB and three developed PD without dementia. The phenoconverter group had significantly lower scores in delayed recall in the memory domain compared to the disease‐free group. Cox hazard analysis showed that MoCA‐J was superior to MMSE.

Conclusions

Among IRBD patients with reduced cardiac MIBG accumulation, MoCA‐J score of <26 (Mild Cognitive Impairment‐Lewy body) and a low sub‐item score for delayed recall predicted short‐term progression to probable DLB.
Multicomponent MR fingerprinting reconstruction using joint‐sparsity and low‐rank constraints
Authors: Nagtegaal Martijn , Hartsema Emiel , Koolstra Kirsten , Vos Frans
Published: September 2022

Purpose

To develop an efficient algorithm for multicomponent MR fingerprinting (MC‐MRF) reconstructions directly from highly undersampled data without making prior assumptions about tissue relaxation times and expected number of tissues.

Methods

The proposed method reconstructs MC‐MRF maps from highly undersampled data by iteratively applying a joint‐sparsity constraint to the estimated tissue components. Intermediate component maps are obtained by a low‐rank multicomponent alternating direction method of multipliers (MC‐ADMM) including the non‐negativity of tissue weights as an extra regularization term. Over iterations, the used dictionary compression is adjusted. The proposed method (k‐SPIJN) is compared with a two‐step approach in which image reconstruction and multicomponent estimations are performed sequentially and tested in numerical simulations and in vivo by applying different undersampling factors in eight healthy volunteers. In the latter case, fully sampled data serves as the reference.

Results

The proposed method shows improved precision and accuracy in simulations compared with a state‐of‐art sequential approach. Obtained in vivo magnetization fraction maps for different tissue types show reduced systematic errors and reduced noise‐like effects. Root mean square errors in estimated magnetization fraction maps significantly reduce from 13.0% 5.8% with the conventional, two‐step approach to 9.6% 3.9% and 9.6% 3.2% with the proposed MC‐ADMM and k‐SPIJN methods, respectively. Mean standard deviation in homogeneous white matter regions reduced significantly from 8.6% to 2.9% (two step vs. k‐SPIJN).

Conclusion

The proposed MC‐ADMM and k‐SPIJN reconstruction methods estimate MC‐MRF maps from highly undersampled data resulting in improved image quality compared with the existing method.
The future is 2D: spectral‐temporal fitting of dynamic MRS data provides exponential gains in precision over conventional approaches
Authors: Tal Assaf
Published: September 2022

Purpose

Many MRS paradigms produce 2D spectral‐temporal datasets, including diffusion‐weighted, functional, and hyperpolarized and enriched (carbon‐13, deuterium) experiments. Conventionally, temporal parameters—such as T2, T1, or diffusion constants—are assessed by first fitting each spectrum independently and subsequently fitting a temporal model (1D fitting). We investigated whether simultaneously fitting the entire dataset using a single spectral‐temporal model (2D fitting) would improve the precision of the relevant temporal parameter.

Methods

We derived a Cramer Rao lower bound for the temporal parameters for both 1D and 2D approaches for 2 experiments: a multi‐echo experiment designed to estimate metabolite T2s, and a functional MRS experiment designed to estimate fractional change () in metabolite concentrations. We investigated the dependence of the relative standard deviation (SD) of T2 in multi‐echo and in functional MRS.

Results

When peaks were spectrally distant, 2D fitting improved precision by approximately 20% relative to 1D fitting, regardless of the experiment and other parameter values. These gains increased exponentially as peaks drew closer. Dependence on temporal model parameters was weak to negligible.

Conclusion

Our results strongly support a 2D approach to MRS fitting where applicable, and particularly in nuclei such as hydrogen and deuterium, which exhibit substantial spectral overlap.
Flow–recruitment relationships for Shoal Chub and implications for managing environmental flows
Authors: Perkin Joshuah S. , Acre Matthew R. , Ellard Johnathan K. , Rodger Anthony W. , Trungale Joeseph F. , Winemiller Kirk O. , Yancy Lauren E.
Published: September 2022

Objective

Regulation of river flow regimes by dams and diversions impacts aquatic biota and ecosystems globally. However, our understanding of the ecological consequences of flow alteration and ecological benefits of flow restoration lags behind our ability to manipulate flows, and there is a need for broader development of flow–ecology relationships. Approaches for establishing flow–ecology relationships have recently shifted away from state-based methods that analyze snapshots of ecological conditions and towards rate-based methods focused on mechanisms that link hydrology with dynamics of important ecological components and processes.

Methods

We used a rate-based approach to validate environmental flow standards developed for the lower Brazos River, Texas, by analyzing the relationship between flow regime components and recruitment strength of imperiled Shoal Chub Macrhybopsis hyostoma, a fluvial specialist and pelagic-broadcast-spawning fish. We collected 254 age-0 Shoal Chub (9–40 mm total length), extracted their otoliths to estimate age in days, and used a generalized additive model to regress the number of captured recruits that hatched on a calendar date against flow regime metrics, such as pulse magnitude, flow rate of change, and pulse timing in relation to environmental flow standards proposed by a science advisory committee (Brazos Basin and Bay Area Expert Science Team).

Result

The model revealed that flow magnitude, rate of change, and timing were all significant predictors that collectively explained 60% of variation in the recruitment strength index. Hindcasting for 1919–2020 showed a general reduction in recruitment strength following commencement of flow regulation in the lower Brazos River and revealed that high recruitment correlated with years in which most or all proposed flow tiers were attained, whereas low recruitment correlated with years when less than half of the targeted tiers were attained.

Conclusion

Our work represents an effective validation method for environmental flow recommendations and reveals specific flow regimes that benefit an imperiled fish species.
Social Fish-Tancing in Wisconsin: The Effects of the COVID-19 Pandemic on Statewide License Sales and Fishing Effort in Northern Inland Lakes
Authors: Trudeau Ashley , Beardmore Ben , Gerrish Gretchen A. , Sass Greg G. , Jensen Olaf P.
Published: September 2022

The first year of the COVID-19 pandemic in 2020 was associated with an “anthropause” in many industries, initially reducing greenhouse gas emissions and other negative anthropogenic influences. However, outdoor recreation has exploded in popularity in response to closures of indoor recreation options, increased free time, and/or increased levels of stress. We tested for the effects of the COVID-19 pandemic on the sale of fishing licenses in Wisconsin and on vehicle counts that were observed at public lake access points in Vilas County, Wisconsin, in 2020. In the summer of 2020, fishing license sales in Wisconsin, USA, increased, particularly among first-time license purchasers for whom cumulative sales in 2020 increased by 71% and 35% compared with the previous 5-year average for Wisconsin residents and nonresidents, respectively. Changes in the vehicle counts at lake access points in the summer of 2020 varied considerably by lake. However, lakes with greater proportions of public shoreline experienced pandemic-associated increases in lake visitors. Our results suggest that the distribution of recreational fishing effort in Wisconsin changed during the pandemic, potentially placing additional harvest pressures on hot spot inland lakes.
Intracerebroventricular administration of oxytocin and intranasal administration of the oxytocin derivative improve β‐amyloid peptide (25–35)‐induced memory impairment in mice
Authors: Takahashi Junpei , Ueta Yudai , Yamada Daisuke , Sasaki‐Hamada Sachie , Iwai Takashi , Akita Tomomi , Yamashita Chikamasa , Saitoh Akiyoshi , Oka Jun‐Ichiro
Published: September 2022

Aim

We previously reported that oxytocin, a peptide hormone, can reverse the β‐amyloid peptide (25–35) (Aβ25–35)‐induced impairments of the murine hippocampal synaptic plasticity. In this study, we examined the effects of oxytocin on the Aβ25–35‐induced impairment of cognitive behavior in murine in order to investigate the potential of oxytocin as a clinical treatment tool for Alzheimer's disease (AD).

Methods

The Y‐maze and Morris water maze (MWM) tests were performed. Since the intracerebroventricular (ICV) administration is both invasive and impractical, we further utilized intranasal (IN) delivery to the brain. For this purpose, we prepared an oxytocin derivative containing cell‐penetrating peptides and a penetration accelerating sequence, which was subsequently used in our IN administration experiments.

Results

We herein showed that the ICV administration of oxytocin in mice exerted memory‐improving effects on the Aβ25–35‐induced amnesia in both the Y‐maze and MWM tests. The IN administration of the oxytocin derivative exhibited memory‐improving effects in the Y‐maze test. Moreover, we acquired evidence that the fluorescein isothiocyanate‐labeled oxytocin derivative was distributed throughout the mouse brain following its IN administration.

Conclusion

Our results suggest that the oxytocin derivative is effective for its IN delivery to the brain and may be particularly useful in the clinical treatment of cognitive impairment, such as that characterizing AD.
Microorganisms swimming through radiative Sutterby nanofluid over stretchable cylinder: Hydrodynamic effect
Authors: Raza Rabeeah , Naz Rahila , Abdelsalam Sara I.
Published: September 2022

In the present article, radiative Sutterby nanofluid flow over a stretchable cylinder is considered. The suspended swimming microorganisms have been deliberated in the fluid analysis. Different processes such as Brownian motion, thermophoresis, Joules heating, and viscous dissipation have been inspected in the presences of stratification parameters. The solutions for flow profiles have been obtained via optimal homotopy analysis method. Impacts of different physical involved variables on non‐dimensional velocity, temperature, nanofluid concentration, and concentration of density of swimming microorganisms have been debated. Coefficient of skin friction, local Nusselt number, Sherwood number, and density of motile organisms have been calculated. The results reveal that Sutterby fluid parameter enhances the skin friction and has a reverse impact on the velocity, while an increase in stratification causes a declination in the flow boundary layers. The temperature of the flow is also seen to be boosted by the increment in Brownian motion parameter. Analysis of entropy generation shows that the concentration difference parameter maximizes the entropy and minimizes the dimensionless Bejan number.
Temporal trends in health worker social media communication during the COVID‐19 pandemic
Authors: Ford Julian D. , Marengo Davide , Olff Miranda , Armour Cherie , Elhai Jon D. , Almquist Zack , Spiro Emma S.
Published: September 2022

During the COVID‐19 pandemic, healthcare professionals are exposed to extreme hazards and workplace stressors. Social media postings by physicians and nurses related to COVID‐19 from January 21 to June 1, 2020 were obtained from the Reddit website. Topic modeling via Latent Dirichlet Allocation (LDA) using a machine‐learning approach was performed on 1723 documents, each posted in a unique Reddit discussion. We selected the optimal number of topics using a heuristic approach based on examination of the rate of perplexity change (RPC) across LDA models. A two‐step multiple linear regression was done to identify differences across time and between nurses versus physicians. Prevalent topics included excessive workload, positive emotional expression and collegial support, anger and frustration, testing positive for COVID‐19 and treatment, use of personal protective equipment, impacts on healthcare jobs, disruption of medical procedures, and general healthcare issues. Nurses' posts initially reflected concern about workload, personal danger, safety precautions, and emotional support to their colleagues. Physicians posted initially more often than nurses about technical aspects of the coronavirus disease, medical equipment, and treatment. Differences narrowed over time: nurses increasingly made technical posts, while physicians' posts increasingly were in the personal domain, suggesting a convergence of the professions over time.
The utility of risk assessment tools for acute pulmonary embolism in children
Authors: Ergenekon Almala P. , Yilmaz Yegit Cansu , Cenk Muruvvet , Gulieva Aynur , Kalyoncu Mine , Selcuk Merve , Dogru Omer , Erdem Eralp Ela , Gokdemir Yasemin , Karakoc Fazilet , Karadag Bulent
Published: September 2022

Background and Aim

Pulmonary embolism (PE) is a potentially life‐threatening disease in children. The objective of the study is to evaluate the utility of adult‐based pulmonary embolism rule‐out criteria (PERC), Pediatric PE Model, and D‐dimer in the diagnosis of PE in children.

Material and Methods

The study consisted of patients under 18 years of age who were consulted to the Pediatric Pulmonology Clinic for the evaluation of PE. Patients were divided into two groups based on the confirmation of PE. The group with the presence of PE (n = 20) consisted of children who were diagnosed with PE. The group with the absence of PE (n = 28) consisted of children with clinically suspected PE but negative diagnostic imaging. Adult validated clinical decision PERC rule and Pediatric PE Model were retrospectively applied to the patients.

Results

In the study, PERC demonstrated a sensitivity of 60% and a specificity of 46% for the diagnosis of PE in children. When PE Model was evaluated for the children, it was found a 50% sensitivity and 75% specificity. Combining PE Model and PERC rule with D‐dimer did not increase the specificity and sensitivity. Smoking was found to be relevant for PE in the childhood. Twenty‐five percent of the patients had a genetic tendency for PE. All of the patients had an underlying disease as well.

Conclusion

None of the current risk assessment tools (PE Model, PERC, D‐dimer) were found to be accurate in predicting PE. Further larger population studies are still required to develop a better diagnostic approach.
Time to second biochemical recurrence as a prognostic indicator in postprostatectomy patients who undergo salvage radiation therapy: An RTOG 9601 based post hoc analysis
Authors: Brodowsky Emily Chan , Sood Akshay , Butaney Mohit , Majdalany Sami E. , Stephens Alex , Corsi Nicholas , Piontkowski Austin J. , Rakic Ivan , Jamil Marcus , Dalela Deepansh , Peabody James O. , Rogers Craig G. , Abdollah Firas
Published: September 2022

Introduction and Objective

The prognostic significance of a “second” biochemical recurrence (sBCR) after salvage radiation therapy (sRT) with/without hormonal therapy following primary radical prostatectomy in men with prostate cancer has not been examined. We hypothesized that a shorter time to sBCR will be associated with worse cancer control outcomes.

Methods

The RTOG 9601 study included 760 patients with tumor stage pT2/T3, pN0, who had either persistently elevated prostate‐specific antigen (PSA) postradical prostatectomy or developed subsequent biochemical recurrence with PSA levels between 0.2 and 4.0 ng/ml. All patients received sRT (with or without 2 years of Bicalutamide) from 1998 to 2015. For our study, we focused on 421 patients who had sBCR after sRT—which was defined as a PSA increase of at least 0.3 ng/ml over the first nadir. Patients were divided into two categories: early sBCR (n = 210) and late sBCR (n = 211) using median time to sBCR (3.51 years). All patients who experienced sBCR received salvage hormonal therapy. Competing‐risk analysis was used to examine the impact of early versus late sBCR on prostate cancer specific mortality (CSM), after accounting for available covariates.

Results

The majority of patients were age 60 years or older (75.8%), had pT3 disease (74.8%), and Gleason score 7 (75.2%). Overall, 13.8% had persistent PSA initially after surgery. At 10 years, starting at the time of sBCR, CSM rate was 31.3% in the early sBCR group versus 20.0% in the late sBCR group. In competing‐risk analysis, time to sBCR was an independent predictor of CSM, where patients with early sBCR had 1.7‐fold higher CSM risk (p = 0.026) than their counterparts with late sBCR.

Conclusions

Time to sBCR after sRT (with or without concomitant Bicalutamide) is a significant predictor of CSM following initial radical prostatectomy. This information can be used to guide subsequent treatments, and to counsel patients.
Effects of a recombinant humanized anti‐cocaine monoclonal antibody on the metabolism and distribution of cocaine in vitro and in mice
Authors: Turner Mackenzie E. , Wetzel Hanna N. , Zinani Dakota B. , Crutchfield Christopher A. , Norman Andrew B.
Published: September 2022

The anti‐cocaine monoclonal antibody, h2E2, is a candidate for treating cocaine‐use disorder. h2E2 binds to and sequesters cocaine in the plasma compartment, effectively decreasing cocaine concentrations in the brains of rats and mice. Despite the binding of cocaine to h2E2, plasma cocaine concentrations decline rapidly in rodents over time, but there was a drastic decrease in the urinary elimination of cocaine in the presence of h2E2. Since cocaine is not being renally excreted, the apparent disappearance of cocaine from the plasma must be explained by either metabolism or distribution. However, binding of cocaine to h2E2 may restrict the availability of cocaine for hydrolysis by endogenous esterases. Therefore, the antibody would be expected to extend the elimination half‐life of cocaine. In contrast, previous studies reported h2E2 as having no effect on the rate of cocaine clearance. It is important to examine the ultimate clearance of the cocaine to ascertain its half‐life and potential for re‐intoxication. Therefore, we investigated the effects of h2E2 on cocaine hydrolysis in vitro and on cocaine metabolism and disposition in vivo over a 6‐h time course. The spontaneous and enzyme‐mediated in vitro hydrolysis of cocaine was drastically decreased in the presence of h2E2 in vitro. Additionally, in mice, h2E2 significantly increased the distribution and elimination half‐lives of cocaine relative to vehicle controls over an extended time course. Therefore, we concluded that h2E2 slowing the distribution and elimination of cocaine is the most appropriate explanation for the initial disappearance of cocaine from the plasma in vivo.
Effect of flavonoid intake on circulating levels of adiponectin and leptin: A systematic review and meta‐analysis of randomized controlled clinical trials
Authors: Liu Xinxin , Yu Zengli , Zhou Huan‐Huan , Feng Yang , Bu Yongjun , Zhai Desheng , Zhang Guofu , Ding Shibin , Wang Erhui , Mi Yang , Wan Zhongxiao
Published: September 2022

This meta‐analysis of randomized controlled trials (RCTs) was conducted to explore the effects of flavonoid intake on adiponectin and leptin levels. The PubMed, EMBASE, and Cochrane Library databases were searched on March 1, 2021. Random‐effects, subgroup, sensitivity, and meta‐regression analyses were conducted on 40 publications. Flavonoid intake significantly increased circulating adiponectin (0.54 μg/ml, 95% CI [0.20, 0.88], p = .002; I2 = 86.4%) and significantly reduced leptin levels (weighted mean difference: −0.79 ng/ml, 95% CI [−1.33, −0.25], p = .004; I2 = 87.7%). Subgroup analysis demonstrated that flavonoid intervention produced a significant elevation in adiponectin levels only in studies that lasted more than 12 weeks, conducted in Asian regions, were parallel‐designed, involved obese or overweight participants and participants with type 2 diabetes mellitus (T2DM) or cardiovascular diseases, used tea catechins, and used a dietary supplement intervention. A significantly negative effect on leptin levels was observed in studies conducted in Asian countries, with healthy participants and participants with T2DM, used whole food interventions, and involved participants with lower baseline leptin levels. In conclusion, flavonoid intake significantly increased circulating adiponectin and decreased leptin levels; however, study heterogeneity was very high. Future well‐designed trials are required to address heterogeneous study designs and clarify the efficacy of plants in regulating adiponectin and leptin levels.
Fulminant streptococcal infection with early immunoglobulin introduction resulting in a favourable outcome for both mother and new‐born: A case report
Authors: Sato Takanori , Oyama Rie , Baba Tsukasa
Published: September 2022

Introduction

The antibacterial agent was changed from cefepime to piperacillin and clindamycin for streptococcal toxic shock syndrome, and an emergency cesarean section was performed. Immunoglobulin was added on the first postoperative day. Group A Streptococcus was isolated on the second postoperative day.

Case

A 37‐year old woman visited her doctor with complaints of sore throat and fever at 32 weeks gestation, she visited her previous doctor for sore throat and fever. She was treated with cefepime and transported to hospital.

Conclusion

Antimicrobial therapy and combined immunoglobulin administration were continued. Both mother and infant survived.
An iterative learning approach to formation control of discrete‐time multi‐agent systems With varying trial lengths
Authors: Liu Yang , Fan Yimin , Ao Yichao , Jia Yingmin
Published: September 2022

In this article, an iterative learning approach is proposed for the formation control of discrete‐time multi‐agent systems, where the trial length of each learning iteration is randomly varying. In particular, a modified state error related to the prescribed formation is defined by taking into account the nonuniform actual trial length that could be different from the desired one. Then, a P‐type iterative learning protocol is established for switching networks of agents subject to nonuniform trial lengths, and the convergence analyses are given for the fixed and the iteration‐varying initial conditions respectively. It shows that through iterative learning, the given formation will be maintained among multiple agents in the entire time interval of one trial. In the end, simulations are done to demonstrate the correctness of the obtained theoretical results.
Dynamic semiparametric transformation models for recurrent event data with a terminal event
Authors: Jin Jin , Song Xinyuan , Sun Liuquan
Published: September 2022

Recurrent event data with a terminal event commonly arise in many longitudinal follow‐up studies. This article proposes a class of dynamic semiparametric transformation models for the marginal mean functions of the recurrent events with a terminal event, where some covariate effects may be time‐varying. An estimation procedure is developed for the model parameters, and the asymptotic properties of the resulting estimators are established. In addition, relevant significance tests are suggested for examining whether or not covariate effects vary with time, and a model checking procedure is presented for assessing the adequacy of the proposed models. The finite sample performance of the proposed estimators is examined through simulation studies, and an application to a medical cost study of chronic heart failure patients is provided.