bluuebunny/crossref_metadata_2025 huggingface dataset:
Therapeutic role of deferred cytoreductive nephrectomy in patients with metastatic renal cell carcinoma treated with nivolumab plus ipilimumab
Authors: Yoshino Maki , Ishihara Hiroki , Nemoto Yuki , Nakamura Kazutaka , Nishimura Koichi , Tachibana Hidekazu , Fukuda Hironori , Toki Daisuke , Yoshida Kazuhiko , Kobayashi Hirohito , Iizuka Junpei , Shimmura Hiroaki , Hashimoto Yasunobu , Tanabe Kazunari , Kondo Tsunenori , Takagi Toshio
Published: July 2022

Objectives

To explore the therapeutic role of deferred cytoreductive nephrectomy in patients with metastatic renal cell carcinoma treated with nivolumab plus ipilimumab.

Patients and methods

Forty-one patients with synchronous metastatic renal cell carcinoma who received nivolumab plus ipilimumab as first-line systemic therapy at our affiliated institutions were retrospectively evaluated. We focused on the prognosis, including tumor responses in primary kidney and metastatic lesions in patients treated with deferred cytoreductive nephrectomy. In addition, the overall survival according to nephrectomy status (i.e. deferred cytoreductive nephrectomy vs. upfront cytoreductive nephrectomy vs. without cytoreductive nephrectomy) was compared.

Results

During a median follow-up period of 12.0 months, seven (30%) patients received deferred cytoreductive nephrectomy at a median time of 10.4 months after nivolumab plus ipilimumab initiation. All the patients showed tumor shrinkage in their primary kidney lesions, including six (86%) patients with ≥30% of shrinkage. Metastatic lesions were also shrunk by ≥30% in six (86%) patients, including two (29%) obtaining complete response. At the last time of follow-up, three (43%) patients were disease-free. The overall survival rate after nivolumab plus ipilimumab initiation tended to be higher in patients with deferred cytoreductive nephrectomy compared with those with upfront cytoreductive nephrectomy (1-year survival rate: 100% vs. 72.4%, P = 0.0587) and those without cytoreductive nephrectomy (vs. 58.2%, P = 0.0613).

Conclusions

The present retrospective data showed that deferred cytoreductive nephrectomy had the potential to exert a therapeutic effect in a subset of patients who obtained favorable tumor responses to nivolumab plus ipilimumab for a certain period. Prospective randomized clinical trials are needed to confirm the prognostic impact of deferred cytoreductive nephrectomy after frontline immunotherapy in synchronous metastatic renal cell carcinoma.
Shrub encroachment threatens persistence of an endemic insular wetland rodent
Authors: Boone Wesley W , Albrecht Audrey A , Conrad Jeremy R , Lechowicz Chris J , Hellgren Eric C , McCleery Robert A
Published: July 2022

Shrub encroachment is altering the structure and species composition of natural communities across the globe. However, little research has focused on how shrub encroachment influences wetland vertebrates, including small mammals. We sought to determine how vegetative structure and shrub cover influenced the occurrence of a threatened semiaquatic mammalian subspecies, the Sanibel Island rice rat (Oryzomys palustris sanibeli). We evaluated the influence of vegetation and metrics of inundation on probability of occurrence and localized seasonal colonization and extinction rates of the Sanibel Island rice rat over a 3-year period. We found Sanibel Island rice rats on 18 (33.3%) of our 54 sites. Their occurrence was positively associated with greater sand cordgrass (Spartina bakeri) cover and increased elevation, but negatively associated with greater shrub cover. Their probability of localized colonization was negatively associated with greater shrub cover. Localized extinction probabilities for Sanibel Island rice rats were positively associated with increased rainfall totals in the preceding 3 months and greater shrub cover. Using aerial photography from across the Sanibel Island rice rat’s range, we found 5.5-fold greater shrub cover in 2015 than in 1944. We suggest that increases in shrub cover and reduced cordgrass cover may be driving the decline of this once ubiquitous endemic species and that the encroachment of freshwater wetlands requires greater attention due to its potential to imperil wetland-dependent wildlife.
Winter torpor and activity patterns of a fishing bat (Myotis macropus) in a mild climate
Authors: Barratt Alice E , Gonsalves Leroy , Turbill Christopher
Published: July 2022

Small insectivorous bats often enter a state of torpor, a controlled, reversible decrease in body temperature and metabolic rate. Torpor provides substantial energy savings and is used more extensively during periods of low temperature and reduced prey availability. We studied torpor use and activity of a small (10.1 ± 0.4 g) fishing bat, Myotis macropus, during winter in a mild climate in Australia. We predicted that the thermal stability of water would make foraging opportunities in winter more productive and consistent in a riparian habitat compared to a woodland habitat, and therefore, fishing bats would use torpor less than expected during winter compared to other bats. Using temperature-sensitive radio transmitters, we recorded the skin temperature of 12 adult (6 M, 6 F) bats over 161 bat-days (13.4 ± 5.4 days per bat) during Austral winter (late May to August), when daily air temperature averaged 6.2–18.2°C. Bats used torpor every day, with bouts lasting a median of 21.3 h and up to 144.6 h. Multiday torpor bouts were more common in females than males. Arousals occurred just after sunset and lasted 3.5 ± 2.9 h. Arousals tended to be longer in males than females and to occur on warmer evenings, suggesting some winter foraging and perhaps male harem territoriality or other mating-related activity was occurring. The extensive use of torpor by M. macropus during relatively mild winter conditions when food is likely available suggests torpor might function to minimize the risks of mortality caused by activity and to increase body condition for the upcoming breeding season.
Carpel-specific down-regulation of GhCKXs in cotton significantly enhances seed and fiber yield
Authors: Zeng Jianyan , Yan Xingying , Bai Wenqin , Zhang Mi , Chen Yang , Li Xianbi , Hou Lei , Zhao Juan , Ding Xiaoyan , Liu Ruochen , Wang Fanlong , Ren Hui , Zhang Jingyi , Ding Bo , Liu Haoru , Xiao Yuehua , Pei Yan
Published: July 2022

Cytokinin is considered to be an important driver of seed yield. To increase the yield of cotton while avoiding the negative consequences caused by constitutive overproduction of cytokinin, we down-regulated specifically the carpel genes for cytokinin oxidase/dehydrogenase (CKX), a key negative regulator of cytokinin levels, in transgenic cotton. The carpel-specific down-regulation of CKXs significantly enhanced cytokinin levels in the carpels. The elevated cytokinin promoted the expression of carpel- and ovule-development-associated genes, GhSTK2, GhAG1, and GhSHP, boosting ovule formation and thus producing more seeds in the ovary. Field experiments showed that the carpel-specific increase of cytokinin significantly increased both seed yield and fiber yield of cotton, without resulting in detrimental phenotypes. Our study details the regulatory mechanism of cytokinin signaling for seed development, and provides an effective and feasible strategy for yield improvement of seed crops.
Cold-mode and hot-mode accretion in galaxy formation: an entropy approach
Authors: Tollet E , Cattaneo A , Macciò A V , Kang X
Published: July 2022

We have analysed two cosmological zoom simulations with $M_{\rm vir}\sim 10^{12}{\rm \, M}_\odot$ from the Numerical Investigation of a Hundred Astrophysical Objects (NIHAO) series, both with and without feedback. We show that an entropy criterion based on the equation of state of the intergalactic medium can successfully separate cold- and hot-mode accretion. The shock-heated gas has non-negligible turbulent support and cools inefficiently. In the simulations without feedback, only a small fraction (≲20 per cent) of the stellar mass comes from baryons that have been in the hot circumgalactic medium, although quantitative conclusions should be taken with caution due to our small-number statistics. With feedback, the fraction is larger because of the reaccretion of gas heated by supernovae, which has lower entropies and shorter cooling times than the gas heated by accretion shocks. We have compared the results of NIHAO to predictions of the GalICS 2.1 semi-analytic model of galaxy formation. The shock-stability criterion implemented in GalICS 2.1 successfully reproduces the transition from cold- to hot-mode accretion.
High-energy γ-ray detection of supernova remnants in the Large Magellanic Cloud
Authors: Campana R , Massaro E , Bocchino F , Miceli M , Orlando S , Tramacere A
Published: July 2022

We present the results of a cluster search in the γ-ray sky images of the Large Magellanic Cloud (LMC) region by means of the Minimum Spanning Tree (MST) and DBSCAN algorithms, at energies higher than 6 and 10 GeV, using 12 yr of Fermi-LAT data. Several significant clusters were found, the majority of which associated with previously known γ-ray sources. We confirm our previous detection of the supernova remnants N 49B and N 63A and found new significant clusters associated with the SNRs N 49, N 186D, and N 44. These sources are among the brightest X-ray remnants in the LMC and corresponds to core-collapse supernovae interacting with dense H ii regions, indicating that a hadronic origin of high-energy photons is the most likely process.
Tobacco Retail Outlets, Neighborhood Deprivation and the Risk of Prenatal Smoke Exposure
Authors: Wheeler David C , Boyle Joseph , Jeremy Barsell D , Maguire Rachel L , Zhang Junfeng (Jim) , Oliver Jason A , Jones Shaun , Dahman Bassam , Murphy Susan K , Hoyo Cathrine , Baggett Chris D , McClernon Joseph , Fuemmeler Bernard F
Published: July 2022

Introduction

Smoking and smoke exposure among pregnant women remain persistent public health issues. Recent estimates suggest that approximately one out of four nonsmokers have measurable levels of cotinine, a marker indicating regular exposure to secondhand smoke. Epidemiological research has attempted to pinpoint individual-level and neighborhood-level factors for smoking during pregnancy. However, most of these studies have relied upon self-reported measures of smoking.

Aims and Methods

To more accurately assess smoke exposure resulting from both smoking and secondhand exposure in mothers during pregnancy, we used Bayesian regression models to estimate the association of cotinine levels with tobacco retail outlet (TRO) exposure and a neighborhood deprivation index (NDI) in six counties in North Carolina centered on Durham County.

Results

Results showed a significant positive association between TRO exposure (β = 0.008, 95% credible interval (CI) = [0.003, 0.013]) and log cotinine after adjusting for individual covariates (eg, age, race/ethnicity, education, marital status). TRO exposure was not significant after including the NDI, which was significantly associated with log cotinine (β = 0.143, 95% CI = [0.030, 0.267]). However, in a low cotinine stratum (indicating secondhand smoke exposure), TRO exposure was significantly associated with log cotinine (β = 0.005, 95% CI = [0.001, 0.009]), while in a high cotinine stratum (indicating active smoking), the NDI was significantly associated with log cotinine (β = 0.176, 95% CI = [0.005, 0.372]).

Conclusions

In summary, our findings add to the evidence that contextual factors are important for active smoking during pregnancy.

Implications

In this study, we found several significant associations that suggest a more nuanced understanding of the potential influence of environmental- and individual-level factors for levels of prenatal smoke exposure. Results suggested a significant positive association between TRO exposure and cotinine levels, after adjusting for the individual factors such as race, education, and marital status. Individually, NDI was similarly positively associated with cotinine levels as well. However, when combining TRO exposure alongside NDI in the same model, TROs were no longer significantly associated with overall cotinine levels.
Isoniazid Adherence Reduces Mortality and Incident Tuberculosis at 96 Weeks Among Adults Initiating Antiretroviral Therapy With Advanced Human Immunodeficiency Virus in Multiple High-Burden Settings
Authors: Gupta Amita , Sun Xin , Krishnan Sonya , Matoga Mitch , Pierre Samuel , McIntire Katherine , Koech Lucy , Faesen Sharlaa , Kityo Cissy , Dadabhai Sufia S , Naidoo Kogieleum , Samaneka Wadzanai P , Lama Javier R , Veloso Valdilea G , Mave Vidya , Lalloo Umesh , Langat Deborah , Hogg Evelyn , Bisson Gregory P , Kumwenda Johnstone , Hosseinipour Mina C ,   for the ACTG A5274/REMEMBER Study Team
Published: July 2022

Background

People with human immunodeficiency virus (HIV) and advanced immunosuppression initiating antiretroviral therapy (ART) remain vulnerable to tuberculosis (TB) and early mortality. To improve early survival, isoniazid preventive therapy (IPT) or empiric TB treatment have been evaluated; however, their benefit on longer-term outcomes warrants investigation.

Methods

We present a 96-week preplanned secondary analysis among 850 ART-naive outpatients (≥13 years) enrolled in a multicountry, randomized trial of efavirenz-containing ART plus either 6-month IPT (n = 426) or empiric 4-drug TB treatment (n = 424). Inclusion criteria were CD4 count <50 cells/mm3 and no confirmed or probable TB. Death and incident TB were compared by strategy arm using the Kaplan-Meier method. The impact of self-reported adherence (calculated as the proportion of 100% adherence) was assessed using Cox-proportional hazards models.

Results

By 96 weeks, 85 deaths and 63 TB events occurred. Kaplan-Meier estimated mortality (10.1% vs 10.5%; P = .86) and time-to-death (P = .77) did not differ by arm. Empiric had higher TB risk (6.1% vs 2.7%; risk difference, −3.4% [95% confidence interval, −6.2% to −0.6%]; P = .02) and shorter time to TB (P = .02) than IPT. Tuberculosis medication adherence lowered the hazards of death by ≥23% (P < .0001) in empiric and ≥20% (P < .035) in IPT and incident TB by ≥17% (P ≤ .0324) only in IPT.

Conclusions

Empiric TB treatment offered no longer-term advantage over IPT in our population with advanced immunosuppression initiating ART. High IPT adherence significantly lowered death and TB incidence through 96 weeks, emphasizing the benefit of ART plus IPT initiation and completion, in persons with advanced HIV living in high TB-burden, resource-limited settings.
Quantitative Analysis of Florigen for the Variability of Floral Induction in Cabbage/Radish Inter-generic Grafting
Authors: Motoki Ko , Kinoshita Yu , Nakano Ryohei , Hosokawa Munetaka , Nakazaki Tetsuya
Published: July 2022

Grafting-induced flowering is a key phenomenon to understand systemic floral induction caused by florigen. It can also be used as a breeding technique enabling rapid seed production of crops with long generation times. However, the degree of floral induction in grafted plants is often variable. Moreover, it is difficult in some crop species. Here, we explored the factors promoting variability in the grafting-induced flowering of cabbage (Brassica oleracea L. var. capitata), an important vegetable crop with a long generation time, via the quantitative analysis of florigen accumulation. Significant variability in the flowering response of grafted cabbage was observed when rootstocks of different genotypes were used. As reported previously, B. oleracea rootstocks did not induce the flowering of grafted cabbage plants, but radish (Raphanus sativus L.) rootstocks unstably did, depending on the accessions used. Immunoblotting analysis of the FLOWERING LOCUS T (FT) protein, a main component of florigen, revealed that floral induction was quantitatively correlated with the level of accumulated FT protein in the grafted scion. To identify rootstock factors that cause variability in the floral induction of the grafted scion, we investigated FT protein accumulation and flowering response in grafted scions when the transcription levels of FT and the leaf area of rootstocks were altered by vernalization, daylength and leaf trimming treatments. We concluded that increasing the total amount of FT protein produced in the rootstock is important for the stable floral induction of the grafted cabbage, and this can be accomplished by increasing FT transcription and the leaf area of the rootstock.
Test–Retest Reliability of a Static and Dynamic Motor Fatigability Protocol Using Grip and Pinch Strength in Children With Cerebral Palsy
Authors: Brauers Lieke , Smeets Rob , Feys Peter , Gordon Andrew M , van der Leij-Roelofsen Bertie , Bastiaenen Caroline , Rameckers Eugene , Klingels Katrijn
Published: July 2022

Objective

The purpose of this study was to investigate the test–retest reliability, measurement error, and interpretability of new motor fatigability outcomes of grip and pinch strength for children with unilateral cerebral palsy (UCP).

Methods

Motor fatigability during grip and pinch strength was measured twice (within 48 hours) in both hands of 50 children (mean age = 11 years 2 months; 14, 31, and 5 children with Manual Ability Classification System levels I, II, and III, respectively) using a 30-second static and dynamic maximum exertion protocol. For static motor fatigability, the Static Fatigue Index (SFI) and mean force (Fmean) in the first (Fmean1) and last (Fmean3) 10 seconds were calculated. For dynamic motor fatigability, Fmean1, Fmean3, and the number of peaks in the first and last 10 seconds were calculated.

Results

For static motor fatigability, the intraclass correlation coefficients (ICCs) were moderate to high for Fmean1 and Fmean3 (0.56–0.88), and the SFI showed low to moderate reliability (ICC = 0.32–0.72). For dynamic motor fatigability, the ICCs were moderate to high for all outcomes (0.54–0.91). The standard error of measurement agreement and the smallest detectable difference agreement were large in all outcomes, except for the SFI in static motor fatigability. Details per age group are provided. In general, younger children (6–11 years old) showed lower reliability than older children (12–18 years old).

Conclusion

Most outcome measures for static and dynamic motor fatigability of grip and pinch strength show moderate to high reliability in children with UCP, indicating that these tests can be used reliably to investigate the presence of motor fatigability in UCP, especially in older children. Standard error of measurement agreement and smallest detectable difference agreement indicated that these outcome measures should be interpreted with caution when evaluating change.

Impact

Most of the proposed outcome measures for static and dynamic motor fatigability of grip and pinch are reliable in children with UCP and can be used for discriminative purposes.
VmMon1-Ccz1 Complex Is Required for Conidiation, Autophagy, and Virulence in Valsa mali
Authors: Xu Liangsheng , Zhang Xiaolong , Zheng Dian , Chang Yali , Zhang Feiran , Wang Yinghao , Huang Lili
Published: July 2022

Apple Valsa canker caused by Valsa mali is a serious disease in eastern Asia, especially in China. In our previous proteomics study, monensin sensitivity 1 protein in Valsa mali ( VmMon1) was identified to be significantly upregulated during V. mali infection. It was reported Mon1 protein formed a heterodimer called MC (Mon1-Ccz1) complex with caffeine, calcium, and zinc sensitivity 1 protein (Ccz1) in yeast. However, Ccz1 had not been identified in plant-pathogenic fungi such as Fusarium graminearum and Magnaporthe oryzae. Here, we identified a Ccz1 ortholog VmCcz1 in V. mali, by using DELTA-BLAST. The interaction of VmMon1 and VmCcz1 were verified using yeast two-hybrid assay, bimolecular fluorescence complementation, and co-immunoprecipitation assays. Further yeast three-hybrid screenings determined that VmRab7 (Ras-related protein in V. mali) interacted with the MC complex. Targeted gene deletion showed that the ∆ VmMon1 and ∆ VmCcz1 mutants were defective in vegetative growth, conidiation, and pathogenicity. In addition, both mutants were more sensitive to osmotic and oxidative stresses and intracellular protein transport inhibitors. Cytological examination revealed that the ∆ VmMon1 and ∆ VmCcz1 mutants were impaired in vacuole fusion and autophagy. More importantly, expression of pectinase genes decreased in both mutants compared with those of the wild type during infection. Overall, our study identified Mon1 and Ccz1 genes in V. mali and provided evidence that VmMon1 and VmCcz1 are critical components that modulate vacuole fusion and autophagy, thereby affecting the development, conidiation, and pathogenicity of V. mali.

[Formula: see text] Copyright © 2022 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .
Bacillus amyloliquefaciens PMB05 Increases Resistance to Bacterial Wilt by Activating Mitogen-Activated Protein Kinase and Reactive Oxygen Species Pathway Crosstalk in Arabidopsis thaliana
Authors: Chuang Chiao-Yu , Lin Si-Ting , Li Ai-Ting , Li Sin-Hua , Hsiao Chia-Yu , Lin Yi-Hsien
Published: July 2022

Bacterial wilt caused by Ralstonia solanacearum can infect many crops, causing significant losses worldwide. The use of beneficial microorganisms is considered a feasible method for controlling this disease. Our previous study showed that Bacillus amyloliquefaciens PMB05 can control bacterial wilt through intensifying immune signals triggered by a pathogen-associated molecular pattern (PAMP) from R. solanacearum. It is still uncertain whether induction of the mitogen-activated protein kinase (MAPK) pathway during PAMP-triggered immunity (PTI) is responsible for enhancing disease resistance. To gain more insights on how the presence of PMB05 regulates PTI signaling, its association with the MAPK pathway was assayed. Our results showed that the activation of MPK3/6 and expression of wrky22 upon treatment with the PAMP, PopW, was increased during co-treatment with PMB05. Moreover, the disease resistance conferred by PMB05 to bacterial wilt was abolished in mekk1, mkk5, and mpk6 mutants. To determine the relationship between the MAPK pathway and plant immune signals, the assay on reactive oxygen species (ROS) generation and callose deposition showed that only the ROS generation was strongly reduced in these mutants. Because ROS generation is highly correlated with RbohD, the results revealed that the effects of PMB05 on both PopW-induced ROS generation and disease resistance to bacterial wilt were eliminated in the rbohD mutant, suggesting that the generation of ROS is also required for PMB05-enhanced disease resistance. Taken together, we concluded that the crosstalk between the initiation of ROS generation and further activation of the MAPK pathway is necessary when PMB05 is used to improve disease resistance to bacterial wilt.

[Formula: see text] Copyright © 2022 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .
The Hidden Disease: Delayed Diagnosis in Duchenne Muscular Dystrophy and Co-Occurring Conditions
Authors: Lee Irene , Turnage Cassie , Sutyla Ryan , Mitchell Paul , Lindahl Hazel , Jesus Anna , Scharf Rebecca J.
Published: July 2022

Objective:

Early diagnosis of Duchenne muscular dystrophy (DMD) is important for timely intervention to prolong function and preserve quality of life. The prevalence of various neurocognitive disorders is known to be higher in patients with DMD than the general population. In this study, we highlight cases of delayed DMD diagnosis that resulted from misattribution of early motor symptoms to co-occurring neurocognitive conditions. We also investigate the difference in age at DMD diagnosis in the setting of specific co-occurring neurocognitive conditions.

Method:

In this study, we reviewed 40 consecutive patients seen at a Certified Duchenne Care Center, excluding siblings of already-diagnosed patients. We highlight cases of significant delay in DMD diagnosis in the setting of co-occurring neurocognitive diagnoses. We also investigate the association of autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD), intellectual disability, and speech/language delay on age of DMD diagnosis.

Results:

The prevalence of co-occurring neurocognitive diagnoses was 73.1% in patients diagnosed at or after age 5 years vs. 35.7% in those diagnosed before age 5 years. The average age of DMD diagnosis was 6.6 years in patients with any co-occurring neurocognitive diagnoses and 4.9 years in patients without (p = 0.09). Individual analysis of ASD and ADHD showed significant differences. A greater number of co-occurring conditions were associated with an increased age at DMD diagnosis (R
2 = 0.87, p < 0.001).

Conclusion:

The data suggest an association between the presence of co-occurring neurocognitive conditions and a later age of DMD diagnosis. One cost-effective diagnostic step that can be implemented by all pediatric practitioners is testing serum creatinine kinase (CK) in any child with motor delays or hypotonia, even in the context of other behavioral or cognitive disabilities.
Straight-tip guidewire versus J-tip guidewire for central venous catheterisation in neonates and small infants
Authors: Kim Eun-Hee , Kang Pyoyoon , Song In Sun , Ji Sang-Hwan , Jang Young-Eun , Lee Ji-Hyun , Kim Hee-Soo , Kim Jin-Tae
Published: July 2022

BACKGROUND

Central venous catheterisation in neonates and infants is challenging because of the small size of the vessels. The curve of the J-tip guidewire causes difficulty when inserting because of the larger radius and the tilted angle of the J-tip.

OBJECTIVE

We hypothesised that a straight-tip guidewire can facilitate guidewire insertion and improve the first-attempt success rate of central venous catheterisation.

DESIGN

A randomised controlled study.

SETTING

This study was performed between September 2018 and July 2021 in tertiary care children's hospital.

PATIENTS

We enrolled infants weighing less than 5 kg undergoing general anaesthesia.

INTERVENTIONS

Patients were randomly allocated to the straight-tip or J-tip groups. Ultrasonography-guided catheterisation was performed using the assigned guidewire.

MAIN OUTCOME MEASURES

The primary outcome was the first-attempt success rate of central venous catheterisation. The secondary outcomes included the number of guidewire insertion attempts, the time required for successful guidewire insertion, and total time for central venous catheter placement.

RESULTS

Eighty-eight patients were studied. The straight-tip group showed a higher first attempt success rate than the J-tip group (86.3 vs. 61.3%, P = 0.007, odds ratio 4.0, 95% confidence interval (CI), 1.4 to 11.4]. Guidewire insertion attempts were higher in the J-tip group than in the straight group (P = 0.002, odds ratio 9.6, 95% CI, 7.9 to 92.9). Although the guidewire insertion time was longer in the J-tip group (P = 0.003, median difference 23.0 s, 95% CI, 7.0 to 48.0), the total catheterisation time was similar owing to the additional guidewire change process in the straight-tip group (P = 0.676).

CONCLUSION

In neonates or infants weighing less than 5 kg, central venous catheterisation using a flexible straight-tip guidewire can improve the first-attempt success rate compared with a J-tip guidewire.

TRIAL REGISTRATION

ClinicalTrials.gov, identifier: NCT03530618.
A new noninvasive finger sensor (NICCI system) for cardiac output monitoring
Authors: Flick Moritz , Jobeir Anas , Hoppe Phillip , Kubik Mathias , Rogge Dorothea E. , Schulte-Uentrop Leonie , Kouz Karim , Saugel Bernd
Published: July 2022

BACKGROUND

The new noninvasive finger sensor system NICCI (Getinge; Gothenburg, Sweden) allows continuous cardiac output monitoring. We aimed to investigate its cardiac output measurement performance.

OBJECTIVE(S)

To investigate the NICCI system's cardiac output measurement performance.

DESIGN

Prospective method comparison study.

SETTING

University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

PATIENTS

Fifty-one patients after cardiac surgery.

MAIN OUTCOME MEASURES

We performed a method comparison study in 51 patients after cardiac surgery to compare NICCI cardiac output (CONICCI) and NICCI cardiac output calibrated to pulmonary artery thermodilution cardiac output measurement (CONICCI-CAL) with pulmonary artery thermodilution cardiac output (COPAT). As a secondary analysis we also compared CNAP cardiac output (COCNAP) and externally calibrated CNAP cardiac output (COCNAP-CAL) with COPAT.

RESULTS

We analysed 299 cardiac output measurement pairs. The mean of the differences (95% limits of agreement) between CONICCI and COPAT was 0.6 (−1.8 to 3.1) l min−1 with a percentage error of 48%. The mean of the differences between CONICCI-CAL and COPAT was −0.4 (−1.9 to 1.1) l min−1 with a percentage error of 29%. The mean of the differences between COCNAP and COPAT was 1.0 (−1.8 to 3.8) l min−1 with a percentage error of 53%. The mean of the differences between COCNAP-CAL and COPAT was −0.2 (−2.0 to 1.6) l min−1 with a percentage error of 35%.

CONCLUSION

The agreement between CONICCI and COPAT is not clinically acceptable.

TRIAL REGISTRATION

The study was registered in the German Clinical Trial Register (DRKS00023189) after inclusion of the first patient on October 2, 2020.
Inhibitory Effect of Essential Oil From Fructus of Alpinia zerumbet on Endothelial-to-Mesenchymal Transformation Induced by TGF-β 1 and Downregulation of KLF4
Authors: Zhang Yanyan , Zhao Shuang , Tu Mengxin , He Li , Xu Yini , Gan Shiquan , Shen Xiangchun
Published: July 2022

Essential oil from fructus of Alpinia zerumbet (EOFAZ) protects vascular endothelial cell (VEC) injury. Stimulation and injury factors can induce phenotypic changes in VECs and the occurrence of endothelial-mesenchymal transformation (EndMT), accelerating the occurrence and development of cardiovascular diseases. We investigated the role of EOFAZ in EndMT induced by transforming growth factor-β1 (TGF-β1). All experiments were performed using human umbilical vein endothelial cells (HUVECs). HUVECs were preincubated with EOFAZ for 2 hours and then coincubated with TGF-β1 for 72 hours. Krüpple-like factor 4 (KLF4) was inhibited by small interfering RNA or overexpressed by adenovirus infection. Wound healing, transwell, and angiogenesis assays were used to evaluate the migration ability of HUVECs. Quantitative RT-PCR and Western blotting were used for mRNA and protein expression analyses, respectively. Immunofluorescence staining was used to detect expression of related markers. A coimmunoprecipitation assay verified the interaction between KLF4 and acetylated histone H3. TGF-β1 contributed to EndMT in HUVECs in a time-dependent manner, mainly manifested as an increase in cell migration ability and changes in the expression of EndMT-related mRNAs and proteins. EOFAZ could inhibit EndMT induced by TGF-β1. The results after transfection with siKLF4 were similar to those of EOFAZ treatment. After EOFAZ treatment, the expression of KLF4 and acetylated histone H3 decreased, and protein interactions between them decreased, while expression of the Notch/Snail signal axis decreased. EOFAZ can attenuate endothelial injuries and suppress EndMT in HUVECs under TGF-β1 stimulation conditions because it may downregulate KLF4, decrease histone H3 acetylation, and inhibit the transduction of the Notch/Snail signaling axis.
Naoxintong Capsule Activates the Nrf2/HO-1 Signaling Pathway and Suppresses the p38α Signaling Pathway Via Estrogen Receptors to Ameliorate Heart Remodeling in Female Mice With Postmenopausal Hypertension
Authors: Cheng Lan , Maboh Rene Nfornah , Wang Huan , Mao Gao-wei , Wu Xiao-ying , Chen Hui
Published: July 2022

Limited treatments are available for alleviating heart remodeling in postmenopausal hypertension. The cardioprotective effect of naoxintong (NXT) has been widely accepted. This study aimed to explore the effects of NXT on pathological heart remodeling in a postmenopausal hypertension mouse model in vivo and H9c2 cardiomyocytes in vitro. In vivo, ovariectomy combined with chronic angiotensin II infusion was used to establish the postmenopausal hypertension animal model. NXT significantly ameliorated cardiac remodeling as indicated by a reduced ratio of heart weight/body weight and left ventricle weight/body weight, left ventricular wall thickness, diameter of cardiomyocytes, and collagen deposition in the heart. NXT also significantly increased the expression of estrogen receptors (ERs) and downregulated the expression of nicotinamide adenine dinucleotide phosphate oxidase 2 (Nox2). In vitro, NXT treatment greatly suppressed angiotensin II–induced cardiac hypertrophy, cardiac fibrosis, and excessive oxidative stress as proven by reducing the diameter of H9c2 cardiomyocytes, expression of hypertrophy and fibrosis markers, intracellular reactive oxygen species, and oxidative enzymes. Mechanistically, NXT significantly upregulated the expression of ERs, which activated the Nrf2/HO-1 signaling pathway and inhibited the phosphorylation of the p38α pathway. Collectively, the results indicated that NXT administration might attenuate cardiac remodeling through upregulating the expression of ERs, which activated the Nrf2/HO-1 signaling pathway, inhibited the phosphorylation of the p38α signaling pathway, and reduced oxidative stress.
The Critical Effect of Bile Acids in Atherosclerosis
Authors: Qi Shangwen , Luo Xu , Liu Shuangfang , Ling Bishi , Jin Hua
Published: July 2022

Atherosclerosis (AS) is one of the most common cardiovascular diseases and is the leading cause of arteriosclerotic cardiovascular disease. Bile acids are not only the products of cholesterol metabolism, but also an important class of signaling molecules. Bile acids exert their biological effects through the bile acid receptor signaling pathways. Bile acid receptors are widely distributed in human organs and tissues. The activation of transcriptional and signaling cascades controls bile acid metabolism and synthesis, lipid and carbohydrate metabolism, immune cell expression, and inflammatory responses. A large body of evidence indicates that bile acids play an important role in the initiation and development of AS, and are strongly associated with AS risk factors. The major bile acid receptors, nuclear receptor farnesoid X receptor (liver) and membrane receptor G protein-coupled receptor 5, exhibit anti-atherosclerotic effects. Other nuclear receptors exert different anti-atherosclerotic or pro-atherosclerotic effects. In this review, we summarize the current knowledge on the effects of bile acids and their receptors in AS and explore the pathway of bile acids involved in atherosclerotic lesions. The main research based on animal models or cell/tissue culture experiments is also discussed. This review provides new ideas for the development of novel therapeutic approaches for AS prevention and treatment.
Contrast-induced Acute Kidney Injury in Diabetic Patients and SGLT-2 Inhibitors: A Preventive Opportunity or Promoting Element?
Authors: Nusca Annunziata , Piccirillo Francesco , Viscusi Michele Mattia , Giannone Sara , Mangiacapra Fabio , Melfi Rosetta , Ricottini Elisabetta , Ussia Gian Paolo , Grigioni Francesco
Published: July 2022

Contrast-induced acute kidney injury (CI-AKI) is a serious complication in patients undergoing diagnostic or therapeutic procedures that require contrast use and negatively affects the long-term outcomes. Patients with type 2 diabetes mellitus (DM), particularly those who have already developed diabetic nephropathy (DN), are more susceptible to contrast-induced renal damage. Indeed, contrast media amplify some pathological molecular and cellular pathways already in place in the DN setting. In recent years, sodium–glucose cotransporter-2 inhibitors (SGLT2i) have triggered a paradigm shift in managing patients with type 2 DM, reducing cardiovascular and renal adverse events, and slowing DN development. Some evidence also suggests favorable effects of SGLT2i on acute kidney injury despite the initial alarm; however, little data exist regarding CI-AKI. The present review provides an updated overview of the most recent experimental and clinical studies investigating the beneficial effects of SGLT2i on chronic and acute renal injury, focusing on their potential role in the development of CI-AKI. Thus, we aimed to expand the clinicians' understanding by underscoring new opportunities to prevent this complication in the setting of DM, where effective preventive strategies are still lacking.
Lessons Learned in Clinical Research Recruitment of Midlife Latinas During COVID-19
Authors: Cortés Yamnia I. , Duran Mayra , Marginean Valentina , Harris Latesha K. , Cazales Andrea , Santiago Lymari , Mislan Margarita Diaz , Perreira Krista M.
Published: July 2022

Objective

The purpose of this brief report is to describe lessons learned in recruiting and enrolling midlife Latinas in a pilot study to reduce cardiovascular disease (CVD) risk during the menopause transition. We also discuss strategies implemented to overcome the challenges presented by the novel coronavirus (COVID-19) pandemic.

Methods

Menopausia, Salud y Corazo´n is a two-group (intervention, waitlist control), repeated measures study. The intervention consists of CVD risk education, coping skills training, physical activity, and stress management. Eligible participants are peri- and early postmenopausal Latinas age 40 to 60 years, free of CVD. From August 2020 to October 2021, we screened 110 women recruited from cultural events and health fairs (n = 56), local businesses (n = 24), and snowball sampling (n = 30). Of these, 60 were eligible for inclusion and 41 enrolled.

Results

Strategies that contributed to successful recruitment included: a primarily Latina bilingual (English, Spanish) research team; flexibility with location and scheduling of data collection; and multiple modes of communication (ie, mailings, phone calls, and text messages). Additionally, we addressed Latino cultural values such as respeto (respect), familismo (loyalty to family), and confianza (trust). In response to COVID-19, we included virtual recruitment strategies, limited in-person visits, and distributed community resources for COVID-19.

Conclusion

We have found that despite the challenges presented by COVID-19, midlife Latinas are receptive to clinical research engagement. Researcher flexibility, multiple recruitment modalities, a bilingual research team, and communication strategies that address cultural values are essential elements for the representation of midlife Latinas in research.
Intermittent feeding and circadian rhythm in critical illness
Authors: Kouw Imre W.K. , Heilbronn Leonie K. , van Zanten Arthur R.H.
Published: July 2022

Purpose of review

Circadian rhythms, i.e., periodic oscillations in internal biological processes, modulate metabolic processes such as hormonal signalling, nutrient absorption, and xenobiotic detoxification. Meal timing is a strong entraining cue for peripheral clocks in various organs, and eating out of circadian phases can impair glucose, gastrointestinal, and muscle metabolism. Sleep/wake cycles and circadian rhythms are extremely disrupted during critical illness. Timing of nutritional support may help preserve circadian rhythms and improve post-Intensive Care Unit (ICU) recovery. This review summarises circadian disruptors during ICU admission and evaluates the potential benefits of intermittent feeding on metabolism and circadian rhythms.

Recent findings

Rhythmic expression of core clock genes becomes rapidly disturbed during critical illness and remains disturbed for weeks. Intermittent, bolus, and cyclic enteral feeding have been directly compared to routine continuous feeding, yet no benefits on glycaemic control, gastrointestinal tolerance, and muscle mass have been observed and impacts of circadian clocks remain untested.

Aligning timing of nutritional intake, physical activity, and/or medication with circadian rhythms are potential strategies to reset peripheral circadian rhythms and may enhance ICU recovery but is not proven beneficial yet. Therefore, selecting intermittent feeding over continuous feeding must be balanced against the pros and cons of clinical practice.
Application of behavioral economics for understanding health behaviors among adolescents and young adults
Authors: Huynh Ashley , Wisk Lauren E.
Published: July 2022

Purpose of review

Behavioral economics (BE) concepts have become well studied tools in addressing patient issues, such as weight loss, smoking cessation, and medication adherence. Although predominantly studied in adult populations, emerging literature has shown BE's utility for adolescent/young adult (AYA) populations, offering a practical framework to safeguard AYA health and influence healthy decision making.

Recent findings

We identified substantive areas in which BE concepts have been applied in AYA populations (e.g., substance use) and outline how these concepts have been used as a tool to identify individuals at risk for poor outcomes and to leverage behavioral insights to improve health behaviors.

BE research holds significant promise as a tool for clinicians and researchers to encourage healthy decision making in AYA populations. Yet, there are opportunities for BE research to expand further into current trends impacting adolescent health, such as electronic nicotine delivery systems, social media apps, and coronavirus disease 2019 vaccinations. Furthermore, the full degree of BE utility remains to be explored, as few studies demonstrate the translation of associative findings into direct interventions. Additional work is needed to formalize BE techniques into best practices that clinicians can implement in their daily practice.
A review on the disparities in the identification and assessment of depression in Black adolescents and young adults. How can clinicians help to close the gap?
Authors: Lemonious Tonya , Codner Michelle , Pluhar Emily
Published: July 2022

Purpose of review

Depression among Black youth has been under-identified, misdiagnosed and undertreated leaving many Black youth to suffer with this potentially debilitating condition. Thus, it is crucial to evaluate how to appropriately identify and treat depression in Black adolescents. This review outlines the risk factors for the development of depression in Black adolescents, the barriers they face when attempting to access mental healthcare and culturally sensitive actions steps a primary care provider can take to help increase the appropriate diagnosis and ultimate treatment of depression in Black adolescents.

Recent findings

Depression can present differently in Black adolescents, which leads to its under identification or misdiagnosis. Moreover, in recent years, the rate of suicide among Black adolescents has been disproportionately rising faster compared to other race/ethnic groups. There have been multiple barriers identified that can be attributed to these findings such as provider mistrust, cultural stigma against seeking help for mental illness, lack of education in the Black community about how depression presents, and lack of financial resources to access mental healthcare.

By understanding the unique experiences and inequities faced by Black youth, a culturally responsive assessment can be performed as the crucial initial step in the diagnostic assessment of their depression.
County-Level Chlamydia and Gonorrhea Rates by Social Vulnerability, United States, 2014–2018
Authors: Copen Casey E. , Haderxhanaj Laura T. , Renfro Kaytlin J. , Loosier Penny S.
Published: July 2022

We examined mean chlamydia and gonorrhea case rates from 2014 to 2018 by categorizing US counties by social vulnerability. Overall, these rates were approximately 1.0 to 2.4 times higher in high vulnerability counties than low vulnerability counties. Percentage change in case rates from low to high social vulnerability counties varied by sex, geographic region, and urbanicity.
Gaps in HIV Preexposure Prophylaxis Continuum of Care Following State Partner Services for Massachusetts Primary and Secondary Syphilis Cases, 2017 to 2018
Authors: Argenyi Michael S. , Molotnikov Lauren E. , Leach Dylan H. , Roosevelt Kathleen A. , Klevens R. Monina , Hsu Katherine K.
Published: July 2022

Background

Human immunodeficiency virus (HIV) preexposure prophylaxis (PrEP) reduces HIV acquisition. We used a PrEP continuum of care to measure impact of field epidemiologist-facilitated referrals for PrEP-naive infectious syphilis cases across multiple clinical and pharmacy sites of care.

Methods

Retrospective analysis of 2017 to 2018 primary and secondary syphilis cases, medical charts, and pharmacy data to identify PrEP education, referral offer, referral acceptance, first visit, prescription pickup (PrEP initiation) and 2 to 3 months (PrEP persistence). The HIV seroconversion was determined using database match at syphilis diagnosis date and at 12 months. χ2 or Fisher’s exact tests were used to compare demographic characteristics associated with steps with lower progression rates.

Results

Of 1077 syphilis cases, partner services engaged 662 of 787 (84%) HIV-negative cases; 490 were PrEP-naive, 266 received education, 166 were offered referral, 67 accepted referral, 30 attended an initial appointment, and 22 were prescribed PrEP. Of 16 with pharmacy data, 14 obtained medication, and 8 persisted on PrEP at 2 to 3 months. Continuum progression was lowest from (1) PrEP-naïve to receiving PrEP education, (2) offered referral to referral acceptance, and (3) referral acceptance to initial PrEP appointment. Men with male partners were more likely to receive PrEP education or accept a referral. Higher social vulnerability was associated with increased PrEP referral acceptance.

Conclusions

Few individuals accepted PrEP referrals and persisted on PrEP. Field and clinic data capture were inconsistent, possibly underestimating referral volume and impact of field engagement. Efforts aimed at increasing referral acceptance and clinic attendance may improve PrEP uptake especially among women and heterosexual men with syphilis.
The Somatoform Spectrum Within the Hierarchical Taxonomy of Psychopathology System: A Taxometric Test of the Latent Structure
Authors: Hartmann Jolina , Bräscher Anne-Kathrin , Forbush Kelsie T. , Sellbom Martin , Watson David , Witthöft Michael
Published: July 2022

Objective

The general understanding of disorders related to chronic somatic symptoms (e.g., somatic symptom disorder, functional somatic syndromes) is limited because of current categorical conceptualizations in traditional taxonomies. To improve clinical utility and validity, the Hierarchical Taxonomy of Psychopathology offers an empirically grounded dimensional approach. Therefore, the distribution of persistent somatic symptom distress observed in nature is highly relevant for informing decisions related to classification and treatment. This study analyzes the underlying structure of symptoms associated with the somatoform spectrum.

Method

Taxometric analyses were used to examine the latent status of the somatoform spectrum, which was measured via a dimensional questionnaire devised as part of the Hierarchical Taxonomy of Psychopathology scale development effort. We generated Comparison Curve Fit Index (CCFI) profile analyses across a clinical sample of psychotherapy outpatients (n = 487), a community sample of German adults (n = 451), and a student sample from New Zealand (n = 549).

Results

In the clinical sample (CCFI mean = 0.38) and in the student sample (CCFI mean = 0.36), a dimensional solution was clearly favored. Results in the community sample (CCFI mean = 0.51) were ambiguous.

Conclusions

Across the three independent samples, qualitatively distinct subgroups within the distribution of chronic somatic symptoms could not be identified. Therefore, continuous representations seemed to best represent the structure of somatic symptoms. Implications of these findings for etiology and treatment are discussed.