bluuebunny/crossref_metadata_2025 huggingface dataset:
Pretrauma risk factors and posttraumatic stress disorder symptoms following subsequent exposure: Multilevel and univariate meta‐analytical approaches
Authors: Georgescu Teodora , Nedelcea Cătălin
Published: September 2023

The endeavour to comprehend why certain individuals develop posttraumatic stress disorder (PTSD) symptoms subsequent to experiencing traumatic events, while others do not, underscores the paramount importance of pretraumatic risk factors. This meta‐analysis summarises the extant results of studies assessing risk factors prior exposure and PTSD symptoms following an index event on the same participants. It includes 43 studies (N = 19,239) yielding 174 effect sizes of pretraumatic risk factors categories such as demographic factors, cognitive factors, personality traits, coping styles, psychopathology, psychophysiological and environmental factors, which were examined using a three‐level meta‐analysis. Additionally, univariate random‐effects meta‐analyses were performed to separately investigate individual risk factors reported in more than one study. The findings revealed significant, small and medium associations for all categories, except for demographic factors and coping styles, also highlighting that certain individual risk factor domains (i.e. previous mental disorders, negative emotionality, sleep complaints and PTSD symptoms) represent the strongest predictors for PTSD symptoms after subsequent exposure. Several moderators were also investigated for individual risk factors. Future research could benefit from considering the interplay of pretraumatic risk factors to draw a more complex picture of the aetiology and underlying mechanisms of PTSD symptoms.
Animal Models for Toxoplasma gondii Infection
Authors: S. Subauste Carlos , Hubal Alyssa
Published: September 2023

Toxoplasma gondii is an obligate intracellular protozoan parasite that commonly infects mammals and birds throughout the world. This protocol describes murine models of acute T. gondii infection, toxoplasmic encephalitis and toxoplasma retinochoroiditis. T. gondii infection in severe combined immunodeficient (SCID) mice, deficient in T and B cells, has allowed for the study of T cell‐independent mechanisms of defense against intracellular organisms, as described here. The uracil auxotroph strain cps1‐1 and temperature‐sensitive mutant strains of T. gondii induce protection against challenge with virulent strains of the parasite. They have allowed studies of immunization and adoptive‐transfer experiments. A protocol is provided for infection with these mutant strains. The EGS strain of T. gondii has the unique feature of spontaneously forming tissue cysts in cell culture. Dual fluorescent reporter stains of this strain have allowed the study of tachyzoite to bradyzoite transitions in vitro and in vivo. A protocol for in vitro and in vivo growth of this strain and tissue cyst isolation is provided. Genetic manipulation of T. gondii and mice has led to the development of parasites that express fluorescent proteins as well as mice with fluorescently labeled leukocytes. This together with the use of T. gondii that express model antigens and transgenic mice that express the appropriate T cell receptor have facilitated the in vivo study of parasite host‐interaction. In addition, parasites that express bioluminescent markers have made it possible to study the dynamics of infection in real time using bioluminescence imaging. Support protocols present methodology for evaluation of progression of infection and immune response to the parasite that includes these newer methodologies. In addition, support protocols address the maintenance of T. gondii tissue cysts and tachyzoites, as well as preparation of T. gondii lysate antigens. © 2023 The Authors. Current Protocols published by Wiley Periodicals LLC.

Basic Protocol 1: Induction of acute T. gondii infection in mice

Basic Protocol 2: Model of toxoplasmic encephalitis and toxoplasma retinochoroiditis in chronically infected mice

Basic Protocol 3: Assessment of T. gondii invasion into neural tissue

Basic Protocol 4: T. gondii infection in scid/scid (SCID) mice

Basic Protocol 5: Infection with the uracil auxotroph strain CPS1‐1 or the temperature‐sensitive TS‐4 strain of T. gondii

Basic Protocol 6: In vivo and in vitro maintenance of the EGS strain of T. gondii

Support Protocol 1: Assessment of progression of infection and immune response to T. gondii

Support Protocol 2: Maintenance of a bank of T. gondii cysts of the ME49 strain

Support Protocol 3: Maintenance of T. gondii tachyzoites using human foreskin fibroblasts

Support Protocol 4: Maintenance of T. gondii tachyzoites in mice

Support Protocol 5: Preparation of T. gondii lysate antigens

Support Protocol 6: Isolation of T. gondii tissue cysts from brain
A transformerless common ground‐based 1‐ϕ single‐stage switched boost inverter for solar photovoltaic applications
Authors: Rage Ravitheja , Sahoo Manoranjan , Thirumala Karthik , Agarwal Soniya
Published: September 2023

This paper proposes a transformerless common ground based single phase single‐stage switched boost inverter for solar photovoltaic (PV) applications. In the proposed inverter, the input DC source and output AC load share a common ground. As a result, the high‐frequency common mode voltage across the parasitic capacitance is eliminated, resulting in negligible leakage current (
) and the associated power loss, and harmonics in the inverter. Moreover, the higher voltage gain of the inverter facilitates the inverter to operate with high modulation index and lower shoot through (ST) duty ratio. Hence, the DC link voltage requirement across the inverter leg is reduced. Consequently, the voltage stress across the switches is minimized. Here, a modified PWM control technique is adopted, where the dual active states of the proposed inverter reduce the inductor current ripple and make it suitable for solar PV applications. The voltage boosting capability of the proposed inverter is extendable with the help of an additional number of intermediate impedance sub‐networks. The detailed steady‐state analysis of the proposed inverter is verified with the help of MATLAB simulation. To verify the simulation results, a 200 W, 120 V, and 50 Hz experimental prototype is developed. The prototype is tested for unity and lagging power factor load conditions with a wide range of input DC voltages, and all the major results are included in the paper. The power and thermal loss analysis is carried out using PLECS software, and the results show that the inverter has a maximum efficiency of 97.48%. From the experimental results, it can be inferred that the proposed inverter has a higher modulation index, lesser inductor current ripple, and zero leakage current as compared to the contemporary inverters.
Individualised adjuvant immunotherapy with neoantigen‐reactive T cells for gastric signet‐ring cell carcinoma
Authors: Ding Naiqing , Liu Qin , Du Juan , Shao Jie , Yang Yang , Yang Ju , Chen Fangjun , Yu Lixia , Liu Baorui , Wei Jia
Published: September 2023

Objectives

The signet‐ring cell carcinoma (SRCC) of the stomach is highly invasive. Patients with stage III gastric SRCC usually experience tumor recurrence within 2 years after radical surgery. Unfortunately, there is no effective treatment to postpone recurrence following adjuvant chemotherapy. Our study aimed to explore the safety and efficacy of neoantigen‐reactive T lymphocytes (NRTs) in patients with stage III gastric SRCC.

Methods

The study included 20 patients with stage III gastric SRCC who received radical surgery and adjuvant chemotherapy. Following the adjuvant chemotherapy, they underwent treatment with a range of one to four cycles of personalised neoantigen‐reactive T cells. The primary endpoint was the median progression‐free survival (mDFS). The secondary endpoint was safety and immune responses. The median duration of follow‐up was 41 months (95% CI: 39–42.9 months).

Results

Our results showed that patients who received adjuvant neoantigen‐reactive T‐cell immunotherapy demonstrated a propensity towards prolonged disease‐free survival (DFS) and overall survival (OS) in comparison to previous studies. The 2‐year DFS and OS rates reached 73.7% and 95%, respectively, whereas the 5‐year DFS and OS rates were 44% and 69%. The median DFS was 41 months (95% CI: 28.9–53.1 months) and the median OS was not reached. In addition, there was a significant increase in serum concentrations of IL‐2, IL‐4, IL‐6, IL‐10, TNF‐α and IFN‐γ after cell immunotherapy. The adverse reactions were mild.

Conclusion

In conclusion, adjuvant immunotherapy with NRTs showed promising efficacy alongside a manageable safety profile.
“You mean it's more than just an eating disorder?”: Commentary on Wade et al. (2023)
Authors: Steiger Howard
Published: September 2023

Drawing from literature on measurement‐based care and prognostic indices in eating disorder (ED) treatment, Wade et al. offer an algorithm for treating co‐occurring mental‐health conditions (i.e., psychiatric comorbidity) in people with EDs, and for studying effects of comorbidity‐oriented treatments. Advocating session‐by‐session measurement to inform adaptive treatment, their proposal outlines a process for adjusting conventional ED treatment to situations in which comorbidity impedes treatment progress. The plan is methodical and responsive to evidence suggesting that peoples' early in‐treatment change has more power, prognostically, than do indices of comorbidity. In the absence of data to inform practices in some areas, the authors intentionally leave key questions unanswered until future results are in. But this means that they reserve comment on how to determine that comorbidity is interfering with treatment response, or to select the best‐fitting of available comorbidity‐oriented options. Likewise, the proposal draws most of its inspiration from literature on individual (mainly cognitive‐behavioral) psychotherapy and, as a result, does not fully represent biopsychosocial perspectives, or elaborate upon the place in comorbidity management of biological treatments, family, and carer involvement, or more complex integrated approaches. Considerations on how to apply the latter methods would broaden the plan's scope.
Development of an integrated modelling framework to evaluate impacts of pressures on habitat conditions and riverine biota
Authors: Chattopadhyay Somsubhra , Szałkiewicz Ewelina , Dytkiewicz Michał , Marcinkowski Paweł , Mirosław‐Świątek Dorota , Oglęcki Paweł , Piniewski Mikołaj
Published: September 2023

It is becoming extremely challenging to protect the structural and functional integrity of freshwater ecosystems, as many ecological systems face pressures from climate change, population growth and other environmental impacts. However, existing approaches of assessing impacts of external stressors to habitat conditions often neglect the long‐term hydrological changes. This study aimed to develop an integrated modelling framework to assess impacts of different stressors on reach‐scale habitat conditions for benthic macroinvertebrates in a temperate lowland river in central Poland. We coupled hydrological (SWAT+), hydraulic (HEC‐RAS 1D and SRH‐2D) and habitat (CASiMiR) models to predict the response of habitat suitability for the functional group of filter feeders to changes in the catchment for a 135‐m section of the Jeziorka river. Setting up and calibrating individual models required extensive field data collection (e.g., bathymetry field surveys, gauging water levels, discharge and flow velocity measurements and biological sampling). The performance of individual models in simulating discharge, water levels and depth/flow velocity was assessed as satisfactory according to literature. The modelling chain was then applied to compare the effects of three flow scenarios (average, low and high flows). The results showed an overall high value of hydraulic habitat suitability index for filter feeders, with moderately and severely lower values for low and high flow scenario, respectively. The implemented modelling framework performed well could be applied to examine the impacts of climate change and other anthropogenic stressors on reach‐scale habitat conditions. Its practical implementation could be beneficial towards sustainable water resources and environmental flow regime development.
Complexity of hydrology, sewage and industries in distribution and migration pathways of heavy metals at spatial scale of China's brownfields
Authors: Yu Jie‐Yu , Wang Jian‐Jian , Zhang Wei , Kattel Giri R. , Kumar Amit , Yu Zhi‐Guo
Published: September 2023

Hydrologic dynamics, sewage and industries determine the distribution and migration pathways of heavy metals in the natural environments including soils across the urbanized area. In this study, 323 stratified soil samples from a brownfield in Jiangsu Province, China, were collected to assess the heavy metals (Cu, Ni, Pb, Cd, As and Hg) contaminations. Contamination factor (Cfi), Nemerow pollution index (PIN) and enrichment factor (EFi) were evaluated to assess the heavy metal pollution, while sources of pollution were identified in combination with geo‐statistical, correlations and principal components analysis. Moreover, transport of Ni in soil profiles over the next 30 years was simulated using HYDRUS. The vertical distribution revealed that the soil surface (0–10 cm) had the highest concentration of heavy metal contamination. ICP‐MS measurements showed that the soil in the brownfield was enriched with Cu, Ni, Pb, Cd, As and Hg, where Ni was the most severe and prevalent contaminant. The results of source apportionment analysis showed that Ni, Cd, Pb and Cu were mainly derived from building materials and sewage discharge, while As and Hg may come from fossil fuel combustion and agricultural discharges from upstream river catchment. The migration of Ni was largely driven by the combination of hydrological variability including the flow and solute contaminant gradients in soils. Our work highlights the need for a comprehensive understanding of the complexity of hydrology, and sewage discharge in heavy metal dynamics and migration pathways in China's brownfield soil at regional and national scales.
Three‐Component Reactions of Quinoxalin‐2(1H)‐ones: Recent Advances
Authors: Wang Ke‐Li , Ji Hong‐Tao , Ou Li‐Juan , He Wei‐Min
Published: September 2023

The multicomponent reactions of quinoxalin‐2(1H)‐ones has attracted considerable interest due to their significant biological and chemical activities. The very recent advances (from 2021 to the beginning of 2023) on the radical three‐component cascade reaction of quinoxalin‐2(1H)‐one derivatives at the C3 position were summarized in this mini‐review. According to the kind of radical types involved, some representative examples and detailed reaction mechanism have been categorized and discussed.

The red front was covered by Figure 1.
Facile Stereoselective Synthesis and Structural Study of Camphor‐ and Fenchone‐Based Spirocyclic 1,3,4‐Oxadiazolines
Authors: Kovaleva Kseniya S. , Abdrakhmanova Veronika S. , Yarovaya Olga I. , Gatilov Yuriy V. , Rybalova Tatyana V. , Salakhutdinov Nariman F.
Published: September 2023

For the first time, an effective method for the synthesis of spirocyclic camphor‐ and fenchone‐based 1,3,4‐oxadiazolines has been developed. The influence of the molecular structure of the terpene substrate on the reaction stereoselectivity was studied. The structural features of the target products were studied using NMR spectroscopy and X‐ray diffraction analysis. The proposed method allows obtaining of spirocyclic products with a wide structural diversity, stereoselectively and in good yields.
Introducing degummed water‐extracted wild almond oil as a safe vegetable oil through the quality evaluation of par‐fried potato sticks and oil thermo‐oxidative stability during a continuous prolonged deep‐fat frying process
Authors: Nekouei Niloufar , Rezaei Karamatollah
Published: September 2023

The purpose of this study is to evaluate the safety of degummed water‐extracted wild almond oil as a frying medium. Changes in the physicochemical properties of the oil as well as those of the fried potato sticks were evaluated over 10 h of frying at 180°C. Compared to a reference commercial frying oil, free fatty acid content, smoke point, anisidine value, conjugated dienes concentration, total polar compounds, color index, and viscosity did not change significantly during the frying process. French fries prepared during the 10 h of frying in the wild almond oil indicated lower fat levels than those prepared in the commercial frying oil. This can contribute to the well‐being of the consumers as well as to the cost‐efficiency of the process. The color indices are additional quality measures for the fried products that were similar for potatoes fried in both oil sources indicating the safe application of water‐extracted wild almond oil for frying purposes. The application of water‐extracted wild almond oil for frying purposes is found to be a safe process to consider in future frying applications.
Dynamic correlations and volatility spillovers between subsectoral clean‐energy stocks and commodity futures markets: A hedging perspective
Authors: Coskun Merve
Published: September 2023

This study investigates the time‐varying connectedness between subsectoral clean‐energy stocks and fossil fuel energy commodities (crude oil, natural gas, and coal) over the period of December 2013–January 2023 employing the Diebold and Yilmaz approach and the dynamic conditional correlation generalized autoregressive conditional heteroscedasticity model. According to the findings, oil transmits the highest volatility spillover shocks to biofuels, and the least to the fuel cell industry. Both natural gas and coal transmit the highest volatility spillover shocks to energy storage, and the least to geothermal and green information technology, respectively. The study also finds strong and time‐varying volatility connectedness among clean‐energy assets and fossil fuels, significantly affected by global extreme events, such as the COVID‐19 pandemic and the Russia–Ukraine conflict. Additionally, the study provides time‐varying and mean optimal hedge ratios with optimal portfolio weights for investors. The empirical results are robust, and important portfolio and policy implications based on empirical findings are provided.
Zircon U–Pb–Hf and whole‐rock Sr–Nd isotopic insights on the Silurian syenite–monzonite shoshonitic magmatism of Central Iran
Authors: Nayebi Niloofar , Raeisi Davood , Babazadeh Shahrouz , Xia Xiao‐Ping , Santosh M.
Published: September 2023

The Palaeozoic magmatic history of Central Iran is related to the subduction of the Proto‐Tethys Ocean and the amalgamation of Gondwana continental fragments. This study presents whole‐rock geochemistry, Sr–Nd isotope and zircon U–Pb–Hf ages of shoshonitic plutonic rocks (e.g., monzonite–syenite) from the north Posht‐e‐Badam (NPB) district with a view to constrain their petrogenetic and tectono‐magmatic evolution during the Palaeozoic. The geochemical data show moderate enrichment in large‐ion lithophile elements and Ti, large positive Pb anomalies, and depletion or moderate enrichment in high‐field‐strength elements (e.g., Nb and Ta), typical of continental arcs. Zircon LA–ICP–MS U–Pb ages are in the range of 444–428 Ma. The Sr–Nd–Hf isotope data, for example, (87Sr/86Sr)i = 0.7073 to 0.7089, εNd(t) = −1.4 to −0.2, and εHf(t) = −3.6 to +7.7, indicate derivation of the magma from a mantle source. The numerical modelling shows a contribution of less than 10% crustal assimilation and ~3% sediment into the melt‐derived mantle. We propose that metasomatic enrichment occurred during the subduction of Proto‐Tethyan Ocean between the Iranian microcontinents, leading to the formation of a shoshonitic melt. We infer that the recorded ages coincide with a continental rift episode followed by a rear arc tectonic region that spread along the northern active margin of Gondwana. Further, the change in magma affinity from calc‐alkaline (~474–512 Ma) to shoshonitic (444–428 Ma) in Central Iran is probably related to the gradual steepening of the slab dip angle and trench‐ward migration of the front arc into the region above metasomatically enriched rear arc mantle.
Long‐term follow‐up of cervical cancer incidence after normal cytological findings
Authors: Wang Jiangrong , Edvardsson Henrik , Strander Björn , Andrae Bengt , Sparén Pär , Dillner Joakim
Published: September 2023

An increase in cervical cancer incidence in Sweden from 2014 to 2015 has been attributed to an increase in false‐negative cytological findings before cancer diagnoses. Years later, we performed a long‐term follow‐up to investigate whether the problem persisted. At each calendar year from 2016 to 2020, we identified women with prior normal cervical screening results through linkage to the Swedish National Cervical Screening Registry. We reported their incidence rates (IRs) of invasive cervical cancer in consecutive years and compared the IRs over time. For the years 2016 to 2020, there was no overall change in cervical cancer incidence after two normal cytology in the last two screening intervals. However, there was a further 62% increase among women 50 to 60 years of age with normal cytology in the past two screening intervals. The incidence rate of cervical cancer was high among nonscreened women and low among HPV‐screened women with negative results, with no trends over time. Our results imply that the previously reported decrease in sensitivity of cervical cytology is persisting. Although primary cytology screening is no longer used, cytology is used in triaging among HPV‐positive women. Our findings suggest that improved triaging is needed, for example, improved quality assurance and/or use of alternative triage tests.
Cushing's syndrome in pregnancy in which laparoscopic adrenalectomy was safely performed by a retroperitoneal approach
Authors: Takeuchi Nobuyoshi , Imamura Yusuke , Ishiwata Kazuki , Kanesaka Manato , Goto Yusuke , Sazuka Tomokazu , Suzuki Sawako , Koide Hisashi , Sakamoto Shinichi , Ichikawa Tomohiko
Published: September 2023

Introduction

Laparoscopic adrenalectomy is the standard treatment for adrenal tumors caused by Cushing's syndrome. However, few pregnant women have undergone adrenalectomy because of the risk of general anesthesia and surgery.

Case presentation

A 28‐year‐old woman presented with gradually worsening Cushing's signs at around 12 weeks of pregnancy. Magnetic resonance imaging displayed a 38‐mm left adrenal tumor, which was the cause of the adrenal Cushing's syndrome. Metyrapone was started, which increased androgen levels. Since the management of Cushing's syndrome by medication alone is challenging, unilateral laparoscopic adrenalectomy by a retroperitoneal approach was performed at 23 weeks of the pregnancy. No perioperative complications were noted.

Conclusion

Adrenalectomy is considered safe in pregnant women with Cushing's syndrome. Laparoscopic adrenalectomy by retroperitoneal approach should be chosen and performed between 14 and 30 weeks of pregnancy to prevent mother and fetal complications.
Does adolescent incivility longitudinally predict future bullying?
Authors: Spadafora Natalie , Volk Anthony A.
Published: September 2023

Introduction

Adolescent bullying is a complicated behavior that is difficult to prevent. Understanding factors that predict bullying during adolescence can help us minimize such behavior. Classroom incivility is a low‐level antisocial behavior that has been discussed in the literature as being a potential predictor of bullying in adolescence. Therefore, the goal of the present study was to examine the longitudinal link between classroom incivility and bullying.

Methods

Data for the current study was collected using quantitative surveys at two‐time points, three years apart (November 2019 and November 2022) in southern Ontario, Canada. Our sample comprised 349 adolescents (51.3% boys, 46.4% girls, 0.6% other, and 1.7% preferred not to say) between the ages of 9 and 14 years old (M = 11.92 years; SD = 1.42). We utilized cross‐lagged analyses to examine the stability of classroom incivility in adolescence, and the longitudinal association between classroom incivility and bullying.

Results

Classroom incivility at Time 1 predicted bullying behavior at Time 2, while bullying at Time 1 did not predict classroom incivility at Time 2. Our results not only support the stability of levels of classroom incivility across time, but also provide empirical support for classroom incivility as a precursor to bullying behavior.

Conclusion

Our study suggests that classroom incivility can not only negatively impact the learning environment but may also be implicated in contributing to the circumstances that promote bullying behavior in adolescence, highlighting the importance of limiting uncivil behavior before it escalates into more severe forms of behavior.
Clinical Pharmacology Profile of AMG 119, the First Chimeric Antigen Receptor T (CAR‐T) Cell Therapy Targeting Delta‐Like Ligand 3 (DLL3), in Patients with Relapsed/Refractory Small Cell Lung Cancer (SCLC)
Authors: Zhou Di , Byers Lauren A. , Sable Beate , Smit Marie‐Anne Damiette , Sadraei Nooshin Hashemi , Dutta Sandeep , Upreti Vijay V.
Published: September 2023

With the promise of a potentially single‐dose curative regimen, CAR‐T cell therapies have brought a paradigm shift in the treatment and management of hematological malignancies with 6 approved products in the USA. However, there are no approved CAR‐T cell therapies for solid tumors. Herein, we report the clinical pharmacology profile of AMG 119, the first CAR‐T cell therapy targeting delta‐like ligand 3 (DLL3), in patients with relapsed/refractory (R/R) small cell lung cancer (SCLC). AMG 119 demonstrated robust cellular expansion with long‐lasting cell persistence and a favorable exposure–response relationship. AMG 119 has been demonstrated to be clinically safe and well tolerated at the doses tested, with no dose‐limiting toxicities (DLTs) reported. This is the first publication of the clinical pharmacology profile of a CAR‐T cell therapy in SCLC, with encouraging cellular kinetics data supporting the potential for CAR‐T cell therapy in solid tumor space.
Target Occupancy and Functional Inhibition of JAK3 and TEC Family Kinases by Ritlecitinib in Healthy Adults: An Open‐Label, Phase 1 Study
Authors: Martin David A. , Telliez Jean‐Baptiste , Pleasic‐Williams Susan , Zhang Ying , Tierney Brendan , Blatnik Matthew , Gale Jeremy D. , Banfield Chris , Zhou Yifan , Lejeune Alexandre , Zwillich Samuel H. , Stevens Erin , Tiwari Neeraj , Kieras Elizabeth , Karanam Ashwin
Published: September 2023

Ritlecitinib is a small molecule in clinical development that covalently and irreversibly inhibits Janus kinase 3 (JAK3) and the TEC family of kinases (BTK, BMX, ITK, TXK, and TEC). This phase 1, open‐label, parallel‐group study assessed target occupancy and functional effects of ritlecitinib on JAK3 and TEC family kinases in healthy participants aged 18‐60 years who received 50 or 200 mg single doses of ritlecitinib on day 1. Blood samples to assess ritlecitinib pharmacokinetics, target occupancy, and pharmacodynamics were collected over 48 hours. Target occupancy was assessed using mass spectroscopy. Functional inhibition of JAK3‐dependent signaling was measured by the inhibition of the phosphorylation of its downstream target signal transducer and activator of transcription 5 (pSTAT5), following activation by interleukin 15 (IL‐15). The functional inhibition of Bruton's tyrosine kinase (BTK)‐dependent signaling was measured by the reduction in the upregulation of cluster of differentiation 69 (CD69), an early marker of B‐cell activation, following treatment with anti‐immunoglobulin D. Eight participants received one 50 mg ritlecitinib dose and 8 participants received one 200 mg dose. Ritlecitinib plasma exposure increased in an approximately dose‐proportional manner from 50 to 200 mg. The maximal median JAK3 target occupancy was 72% for 50 mg and 64% for 200 mg. Ritlecitinib 50 mg had >94% maximal target occupancy of all TEC kinases, except BMX (87%), and 200 mg had >97% for all TEC kinases. For BTK and TEC, ritlecitinib maintained high target occupancy throughout a period of 48 hours. Ritlecitinib reduced pSTAT5 levels following IL‐15‐ and BTK‐dependent signaling in a dose‐dependent manner. These target occupancy and functional assays demonstrate the dual inhibition of the JAK3‐ and BTK‐dependent pathways by ritlecitinib. Further studies are needed to understand the contribution to clinical effects of inhibiting these pathways.
Effect of diabetes mellitus on association between galectin‐3 andH2FPEFscore in patients with unexplained dyspnea and a preserved left ventricular ejection fraction
Authors: Dogdu Orhan , Karasu Mehdi , Karaca Yücel , Harman Murat
Published: September 2023

Objectives

The aim of this study was to investigate the effect of diabetes mellitus (DM) on the association between Galectin‐3 (Gal‐3) and the H2FPEF score in patients with unexplained dyspnea and a preserved left ventricular ejection fraction (LVEF).

Methods

A cross‐sectional observational study was conducted on patients with unexplained dyspnea and a preserved LVEF in the Cardiology Department of Elazıg Medical Park Hospital, Turkey. The patients were evaluated based on the presence of DM and the H2FPEF score. Gal‐3 levels were compared between groups, and the effect of DM on Gal‐3 was assessed. The level of statistical significance in all tests was set atp < .05.

Results

Gal‐3 and H2FPEF scores were higher in patients with DM (p < .001 andp = .027, respectively). Gal‐3 and HbA1C values were elevated in patients with moderate to high H2FPEF scores (p < .01 andp = .036, respectively). DM and Hypertension were more prevalent in patients with moderate to high H2FPEF scores (p = 0.024,p < 0.001, respectively). A strong correlation was observed between Gal‐3 and the H2FPEF score (r = 0.375,p < .001). Gal‐3 could predict patients with a moderate to high H2FPEF score using a cut‐off value of 14.7, with a sensitivity of 69% and specificity of 67% (AUC: 0.702).

Conclusions

Gal‐3 serves as an independent predictor of the H2FPEF score in the presence of DM, and the diagnostic capability of Gal‐3 for Heart Failure with preserved LVEF remains unaffected by DM.
Preliminary PET imaging of [11C]evobrutinib in mouse models of colorectal cancer, SARS‐CoV‐2, and lung damage: Radiosynthesis via base‐aided palladium‐NiXantphos‐mediated 11C‐carbonylation
Authors: Boyle Amanda J. , Lindberg Anton , Tong Junchao , Zhai Dongxu , Liu Fang , Vasdev Neil
Published: September 2023

Evobrutinib is a second‐generation, highly selective, irreversible Bruton's tyrosine kinase (BTK) inhibitor that has shown efficacy in the autoimmune diseases arthritis and multiple sclerosis. Its development as a positron emission tomography (PET) radiotracer has potential for in vivo imaging of BTK in various disease models including several cancers, severe acute respiratory syndrome‐coronavirus‐2 (SARS‐CoV‐2), and lipopolysaccharide (LPS)‐induced lung damage. Herein, we report the automated radiosynthesis of [11C]evobrutinib using a base‐aided palladium‐NiXantphos‐mediated 11C‐carbonylation reaction. [11C]Evobrutinib was reliably formulated in radiochemical yields of 5.5 ± 1.5% and a molar activity of 34.5 ± 17.3 GBq/μmol (n = 12) with 99% radiochemical purity. Ex vivo autoradiography studies showed high specific binding of [11C]evobrutinib in HT‐29 colorectal cancer mouse xenograft tissues (51.1 ± 7.1%). However, in vivo PET/computed tomography (CT) imaging with [11C]evobrutinib showed minimal visualization of HT‐29 colorectal cancer xenografts and only a slight increase in radioactivity accumulation in the associated time‐activity curves. In preliminary PET/CT studies, [11C]evobrutinib failed to visualize either SARS‐CoV‐2 pseudovirus infection or LPS‐induced injury in mouse models. In conclusion, [11C]evobrutinib was successfully synthesized by 11C‐carbonylation and based on our preliminary studies does not appear to be a promising BTK‐targeted PET radiotracer in the rodent disease models studied herein.
Hematopoietic stem cell transplant does not prevent neurological deterioration in infants with Farber disease: Case report and literature review
Authors: Goudie Catherine , Alayoubi Abdulfatah M. , Tibout Pauline , Duval Michel , Maranda Bruno , Mitchell David , Mitchell John J.
Published: September 2023

Farber disease (FD) is an inherited autosomal recessive disorder of lipid metabolism. The hallmark of the disease is systemic accumulation of ceramide due to lysosomal acid ceramidase deficiency. The involvement of the central nervous system is critical in this disorder leading to rapid deterioration and death within a few years after birth. Efforts to treat patients by hematopoietic stem cell transplant (HSCT) have resulted in favorable results in the absence of neurological manifestations. We report the outcomes of HSCT in two patients with FD who received early HSCT and had neurological deterioration posttransplant. We also present a new understanding of the limitations of HSCT in FD management based on our observations of the clinical course of the two patients after therapy.
Palaeoenvironmental reconstruction of Loch Duart (NW Scotland, UK) since the Last Glacial Maximum: implications from a multiproxy approach
Authors: Taylor Jennifer , Selby David , Lloyd Jeremy M. , Podrecca Luca , Masterson Andrew L. , Sageman Bradley B. , Szidat Sönke
Published: September 2023

A sediment core from the salt marsh fringing Loch Duart, NW Scotland, UK, containing Lateglacial to Holocene sediments, was analysed using a multi‐element geochemical approach to elucidate the relative sea level (RSL) and palaeoenvironmental changes associated with the deglaciation of the British and Irish Ice Sheet. Elemental and isotopic measurements of rhenium, osmium, carbon and nitrogen, X‐ray fluorescence scanning, radiocarbon dating, and foraminiferal analysis produced a suite of data that complements the existing biostratigraphic framework. This suite of bio‐, litho‐ and chemostratigraphic analyses permits discussion of RSL changes that reflect the interplay between post‐glacial eustatic rise and glacio‐isostatic adjustment. The osmium‐isotope (187Os/188Os) data, coupled with a new age–depth model, depict an RSL fall between 16.8 and 14.1 ka cal
bp at an average rate of 2 mm a−1. Falling RSL culminates in basin isolation and is followed by subsequent marine inundation from 11.6 ka cal
bp. This RSL record preserves the local interaction between glacial isostatic adjustment and glacio‐eustatic sea‐level change, a relationship that is reflected in the sediment's 187Os/188Os signature. This is the first known application of the osmium isotope system in an isolation basin that is shown to be a viable proxy for RSL change, a technique that could be applied to glacially influenced isolation basins globally.
Relation between quantitative descriptive analysis and textural analysis of boiled plantain
Authors: Newilah Gérard Ngoh , Kendine Vepowo Cédric , Ngouno Annie Takam , Kamgo Dallonnes Fangueng , Nzimi Raymonde Nya , Tembe Jonas Tembe , Ngombi Eric Ngombi , Gouado Inocent , Deuscher Zoé , Bouniol Alexandre , Ayetigbo Oluwatoyin , Dufour Dominique
Published: September 2023

BACKGROUND

Inadequate consideration of textural quality in conventional breeding pipelines of plantains (from breeders to end‐users) results in limited impact. Knowledge of the textural quality characteristics of boiled plantain, as preferred by end‐users, could help improve the adoption of new clones when these traits are selected for breeding. The present study aimed to evaluate the relationship between instrumental and sensory texture attributes of boiled plantain genotypes. Consumer testing (Just About Right and Check All That Apply tests), sensory quantitative descriptive analysis (QDA), instrumental texture profile analysis (TPA) and penetrometry were conducted with nine accessions: three landraces and six plantain‐like bred hybrids.

RESULTS

Landraces were considered just‐about‐right by more than 45% of people for all the sensory attributes (humidity, sweetness, color and firmness), described by characteristics such as smooth on sight, attractive, mealy, firm, plantain taste and yellow. Color and firmness were the most highly scored attributes by panelists for the landraces. Penetrometry discriminated among genotypes better than TPA. Hardness, gumminess, resilience and chewiness were the most discriminatory attributes for TPA, whereas hardness and area under the curve were the most discriminatory attributes for penetrometry. No correlation was found between penetrometry and sensory texture of boiled plantain. For TPA, negative correlations were found between sensory humidity and hardness, as well as between sensory firmness and resilience, whereas a positive correlation was found between resilience and sensory humidity.

CONCLUSION

Combining QDA and texture measurements can make the selection of plantain hybrids more effective and improve the adoption of new varieties. © 2023 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.
Polycarbonate‐coated magnetic nanoparticles for the extraction of imipramine and its primary metabolite from urine
Authors: Sattari Dabbagh Masoumeh , Farajzadeh Mir Ali , Pirmohamadlou Alireza , Manafi Khoshmanesh Sara , Hamishehkar Hamed
Published: September 2023

This study introduces a reliable and inexpensive magnetic dispersive solid phase extraction to extract imipramine and its primary metabolite (desipramine) from urine samples. To accomplish this aim, Fe3O4 magnetic nanoparticles were synthesized by sonication, subsequently, polycarbonate was precipitated gradually onto the surface of them to form the adsorbent. Extraction recoveries of 85% and 76%, enrichment factors of 57 and 51, limits of detection of 2.5 and 2.8 μg/L, and limits of quantification of 8.3 and 9.3 μg/L were obtained for imipramine and desipramine under the optimal conditions, respectively. In addition, relative standard deviations for intra‐ (n = 6) and inter‐day (n = 5) precisions at two concentrations (50 and 100 μg/L of each analyte) were less than or equal to 4%. Short extraction time, good repeatability, high enrichment factors, and simplicity are the main advantages of the proposed method.
Alfalfa–organic amendments impact soil carbon sequestration and its lability in reclaimed loess
Authors: Yelikbayev B. K. , Pagano M. C. , Mamedov A. I. , Islam K. R.
Published: September 2023

Soils derived from loess are fertile but susceptible to accelerated degradation in response to agricultural practices. The objective of our study was to evaluate the long‐term effects of alfalfa (Medicago sativa L.) integrated with contrasting organic amendments (29 years) to rejuvenate degraded loess via total soil organic carbon (SOC) sequestration. The replicated study was conducted in concrete lysimeter plots (2 m long × 1 m wide × 60 cm deep) filled with degraded loess materials followed by planting of alfalfa with cattle manure (60 Mg/ha) or vermicompost (27 Mg/ha) amendments. After 29 years, SOC concentration increased by 5.3–6.2‐fold under alfalfa–organic amendments compared to the control. A similar impact of alfalfa–organic amendments was observed on the humic acid, fulvic acid, and humin concentrations. There was an overestimation of SOC stocks (151 ± 48 kg/ha) when equivalent depth was used compared to equivalent mass of soil. While the SOC sequestration rates were 614 ± 129, 710 ± 69, and 744 ± 161 kg/ha/year at 0–10 cm depth under alfalfa, alfalfa–manure, and alfalfa–vermicompost treatments, respectively, the SOC sequestration rates decreased with depth. Significantly higher values of carbon pool index (CPI) and carbon management index (CMI) under alfalfa–organic amendments justified our results associated with the SOC sequestration; however, the SOC lability (CL) decreased under alfalfa–organic amendments, when compared to the control. A significant nonlinear inverse relationship (R2 = 0.80) between the CPI and CL suggested that SOC sequestration is significantly dependent on its lability or vice versa. Our results suggested that the impact of alfalfa–organic amendments significantly rejuvenated the degraded loess soils via SOC sequestration.
Ultra‐Low Loss SiN Edge Coupler for III‐V/SiN Hybrid Integration
Authors: He An , Cui Yiou , Xiang Jinlong , Wei Wenqi , Wang Zihao , Wang Ting , Guo Xuhan , Su Yikai
Published: September 2023

Silicon photonics is becoming a competitive technology to settle the issues of power and speed in data centers and computing systems. However, the absence of an on‐chip light source restricts the wide and deep application of silicon photonics. Essentially, efficient edge coupling from a Si‐based III‐V laser to silicon photonic components remains the major obstacle for on‐chip integration. Here, two compact edge couplers with ultra‐low coupling loss and eased fabrication for the light transmission from a Si‐based III‐V laser to Si3N4 waveguide are realized. An ultra‐low laser‐to‐chip coupling loss of only 1.175 dB for the butt coupling of a Si‐based InAs QD laser is experimentally demonstrated with high alignment tolerance. The strategies presented here provide a competitive solution for realizing ultra‐efficient integration of Si‐based light sources and silicon photonic components.
It's the smallness that counts: Consumer preferences for small versus large companies' products
Authors: Uzdavinyte Elze , Baršytė Justina , Kaminskiene Zivile
Published: September 2023

Previous research has repeatedly suggested that small (vs. large) companies have a higher appeal to consumers, yet the underlying mechanisms explaining why such an effect occurs remain understudied. Through four experiments, we show that company size cues affect consumer preferences; products originating from small companies are perceived to be healthier than those from large companies, with a downstream positive effect on willingness to buy. Specifically, small (vs. large) company size cues increase the perception of product safety, in turn increasing the perception of product healthiness. This effect is more pronounced for individuals who are more sensitive to safety signals, scoring high on sensitivity to pathogen disgust. Our findings provide managerially relevant insights and show that additional safety‐related signals have the potential to counteract this seemingly inherent disadvantage for large companies.
The Role of Tryptophan Metabolism in the Occurrence and Progression of Acute and Chronic Kidney Diseases
Authors: Hui Yueqing , Zhao Jin , Yu Zixian , Wang Yuwei , Qin Yunlong , Zhang Yumeng , Xing Yan , Han Mei , Wang Anjing , Guo Shuxian , Yuan Jinguo , Zhao Yueru , Ning Xiaoxuan , Sun Shiren
Published: September 2023

Acute kidney injury (AKI) and chronic kidney disease (CKD) are common kidney diseases in clinics with high morbidity and mortality, but their pathogenesis is intricate. Tryptophan (Trp) is a fundamental amino acid for humans, and its metabolism produces various bioactive substances involved in the pathophysiology of AKI and CKD. Metabolomic studies manifest that Trp metabolites like kynurenine (KYN), 5‐hydroxyindoleacetic acid (5‐HIAA), and indoxyl sulfate (IS) increase in AKI or CKD and act as biomarkers that facilitate the early identification of diseases. Meanwhile, KYN and IS act as ligands to exacerbate kidney damage by activating aryl hydrocarbon receptor (AhR) signal transduction. The reduction of renal function can cause the accumulation of Trp metabolites which in turn accelerate the progression of AKI or CKD. Besides, gut dysbiosis induces the expansion of Enterobacteriaceae family to produce excessive IS, which cannot be excreted due to the deterioration of renal function. The application of Trp metabolism as a target in AKI and CKD will also be elaborated. Thus, this study aims to elucidate Trp metabolism in the development of AKI and CKD, and explores the relative treatment strategies by targeting Trp from the perspective of metabolomics to provide a reference for their diagnosis and prevention.
The complexity of patient adherence in orthopaedics: A qualitative study to identify barriers and develop strategies for adherence partnerships
Authors: Rucinski Kylee , Cook James L. , Royse Lisa A.
Published: September 2023

Introduction

While the importance of patient adherence to treatment protocols is firmly accepted, a definition for adherence and mechanisms to address non‐adherence are not well established. The goals of this study were to define adherence and identify barriers and enablers for adherence partnerships through the lens of the orthopaedic healthcare team.

Methods

The qualitative study was designed using concepts from grounded theory.

Eight focus groups, comprised of orthopaedic healthcare team members, were conducted to identify factors influencing orthopaedic patient adherence to treatment plans.

Results

Healthcare team members identified a range of factors affecting patient adherence. Participants conveyed that patient non‐adherence can be a deliberate decision but can also result from barriers faced by the patient. Synthesis of themes identified distinct phases of adherence and culminated in the creation of a preliminary model that encapsulates healthcare team and patient factors impacting adherence, which was entitled, The Barriers and Enablers to Treatment Adherence (BETA) Model.

Conclusion

The study findings alleviate the patient from the sole burden of adherence, recognising the influences that the healthcare team and system have on patients' ability to adhere. The BETA model of patient adherence represents the first step to mitigating non‐adherence by providing a foundation for programmatic research aimed at developing and evaluating interventions and management strategies that empower healthcare teams to effectively equip patients for adherence, leading to optimised patient outcomes following orthopaedic interventions.
Estimates of adult Lake Trout mortality from coded wire tags in a population with developing natural reproduction in southern Lake Michigan
Authors: Clark Richard D. , Ebener Mark P. , Bence James R. , Kornis Matthew S. , Bronte Charles R. , Treska Theodore J. , Jonas Jory L. , Madenjian Charles P. , Tsehaye Iyob W.
Published: September 2023

Objective

Overfishing and Sea Lamprey Petromyzon marinus predation led to extirpation of Lake Trout Salvelinus namaycush from Lake Michigan in the 1950s. Large populations of hatchery-reared fish were developed by the 1970s, but natural reproduction was limited until the early 2000s when it began to increase in the southern main basin. Hypothesizing that the relatively low mortality of spawning-aged fish contributed to this reproductive success, we estimated the total annual mortality rate for this population.

Methods

We used catch curves to estimate the total instantaneous mortality rate Z using coded wire tags, which provided definitive ages. We made separate estimates from fish collected in three on-going surveys: a spring gill-net survey, a fall gill-net spawning survey, and a sport fishery survey.

Result

Our estimates of Z ± SE were 0.297 ± 0.019, 0.239 ± 0.009, and 0.205 ± 0.007 for the spring, spawning, and sport fishery surveys, respectively. We suggest that the mean Z ± SE of all survey estimates of 0.247 ± 0.027 would be a reasonable estimate for this population, which equates to a total annual mortality of 22 ± 3%. This estimate is in the low range of rates reported for the species and is in the same range as other populations in the Great Lakes with well-established natural reproduction.

Conclusion

We concluded that these low total mortality rates contributed to the reproductive success in southern Lake Michigan through increasing spawning stock density and age structure and that previous estimates of another important population parameter, the instantaneous natural mortality rate M, were too high. Estimates of M ranged from 0.210 to 0.240 and were based on the Pauly equation, a growth- and temperature-based estimator. We suggest maximum-age-based estimators of M are more appropriate for Lake Trout. Several alternative maximum-age-based estimators produced estimates for M of 0.132–0.058, all of which are more compatible with our estimate of Z.