bluuebunny/crossref_metadata_2025 huggingface dataset:
Intrauterine and Lactational Exposure to Paracetamol: Cardiometabolic Evaluation in Adult Female and Male Offspring
Authors: Novi Daniella R. B. S. , Vidigal Camila B. , Moura Kawane F. , da Silva Deborah G. , Serafim Ana Flavia L. , Klein Rodrigo M. , Moreira Estefânia G. , Gerardin Daniela C. C. , Ceravolo Graziela S.
Published: October 2021

Paracetamol (PAR) is the most common over-the-counter drug recommended by physicians for treatment of pain and fever during gestation. This drug is not teratogenic, being considered safe for fetus; however, PAR crosses the blood–placental barrier. Considering that, the present study aimed to evaluate the vascular and metabolic safety of PAR exposure during intrauterine and neonatal development in adult male and female-exposed offspring. Wistar female rats were gavaged, with PAR (350 mg/kg/d), from gestational day 6–21 or from gestational day 6 until postnatal day 21. Control dams received water by gavage at the same periods. The male and female offspring were evaluated at adulthood (80 days of life). The thoracic aorta reactivity to acetylcholine, sodium nitroprusside, and phenylephrine was evaluated in male and female adult offspring. It was observed that aortic relaxation was similar between the PAR and control offspring. In addition, the contraction to phenylephrine was similar between the groups. Further, the insulin sensitivity, adipose tissue deposition and blood pressure were not different between PAR and control adult offspring. These results suggest that the protocol of PAR exposure used in the present study did not program vascular and metabolic alterations that would contribute to the development of cardiometabolic diseases in adult life, being safe for the exposed offspring.
Pain management in outpatient surgical abortion
Authors: Liu Serena M. , Shaw Kate A.
Published: October 2021

Purpose of review

To review the current literature focusing on pain management and experiences during abortion care.

Recent findings

Analgesic options in abortion care address pain associated with the procedure, osmotic dilator insertion, and cervical preparation. The paracervical block (PCB) is effective for pain control in first and second trimester abortions. Lower volume PCBs demonstrate non inferiority with osmotic dilator placement compared with higher volume PCBs with lower potential for toxicity. Self-administered vaginal lidocaine gel is noninferior to PCB in first trimester abortions. Preoperative oral narcotics and sedation do not reduce pain in first trimester abortions; however, the latter may reduce anxiety. For second trimester abortions, narcotics or gabapentin do not improve postoperative pain, yet up to half of patients will use narcotics if offered. Nonpharmacological methods have shown success in pain management. Music and doula support do not improve pain; however, patients would recommend these modalities, indicating some benefit that went unmeasured. Auricular acupuncture and transcutaneous electrical nerve stimulation (TENS) reduce pain and anxiety during first trimester abortions.

Several modalities reduce pain during abortion care; however, pain alone does not reflect patient satisfaction. Development of multidimensional measures for pain control assessment has the potential to capture the patient's overall experience.
Current and future transcatheter aortic valve replacement valves
Authors: Eikelboom Rachel , Moran Ricky Muller , Yan Weiang , Yamashita Michael , Patel Apurva , Reardon Michael , Spooner Aaron
Published: October 2021

Purpose of review

This review analyzes currently available commercial transcatheter aortic valve replacement (TAVR) valves as well as valves in investigational status and those in preclinical testing. The design features and clinical outcomes of the Edwards SAPIEN S3 and Medtronic Evolut PRO+ are described and compared with highlight clinical circumstances where one may be favoured over the other.

Recent findings

Multiple randomized and nonrandomized trials have compared commercial and investigational TAVR valves. The results of these are summarized and discussed within this review with a focus on how the SAPIEN S3 and Evolut PRO+ both compare to each other as well as various valves in different investigational stages.

TAVR is an innovative and ground-breaking technology that will forever have revolutionized the management of aortic stenosis. Though the technology and valves themselves have come a long way, further developments are necessary if we are to continue to expand its indications and achieve a safer perioperative experience with more durable valves.
Nondiffractive wavefront-shaping extended depth-of-focus intraocular lens: visual performance and patient-reported outcomes
Authors: Kohnen Thomas , Petermann Kerstin , Böhm Myriam , Hemkeppler Eva , Ahmad Wasim , Hinzelmann Lisa , Pawlowicz Katarzyna , Jandewerth Tyll , Lwowski Christoph
Published: October 2021

Purpose:

To evaluate visual performance and patient-reported outcomes after bilateral implantation of a new nondiffractive wavefront-shaping extended depth-of-focus (EDoF) intraocular lens (IOL).

Setting:

Department of Ophthalmology, Goethe University, Frankfurt, Germany.

Design:

Prospective, single-arm, single-center study.

Methods:

Patient population: 16 patients (32 eyes) who received bilateral implantation of a nondiffractive wavefront-shaping EDoF IOL (AcrySof IQ Vivity) were included. Target refraction in both eyes was emmetropia. Observation procedure: Monocular and binocular uncorrected (UCVA) and distance-corrected (DCVA) visual acuity (VA), refractive outcome, defocus curve, and contrast sensitivity (CS) were evaluated 3 months after surgery with a questionnaire on optical phenomena and spectacle independence. Main outcome measure: 3-month postoperative monocular and binocular UCVA and CDVA (logMAR), defocus curve, CS, and quality of vision (QoV) questionnaire results.

Results:

16 patients with 32 eyes were included. Mean spherical equivalent was −0.16 ± 0.37 diopters (D) 3 months postoperatively. Binocular uncorrected distance VA at distance, intermediate, and near was 0.01 ± 0.05 logMAR at 4 m, 0.05 ± 0.05 logMAR at 80 cm, 0.07 ± 0.06 logMAR at 66 cm, and 0.25 ± 0.11 logMAR at 40 cm, respectively. Despite some minor optical phenomena, 88% of patients would choose the same lens. 63% of patients reported no optical phenomena at all. CS was 1.25 ± 0.41 logCS (photopic), 0.96 ± 0.24 logCS (mesopic), and 0.93 ± 0.24 (mesopic + glare).

Conclusions:

This nondiffractive wavefront-shaping EDoF IOL provides good VA at far and intermediate distance and functional near VA. It showed good QoV and CS and high spectacle independence for distance and intermediate vision with significantly less optical phenomena than with other EDoF or multifocal IOLs.
Intraoperative complications and visual outcomes of cataract surgery in patients with retinal vein occlusion: multicenter database study
Authors: Ponder Christian M. , Rather Peyton A. , Soliman Mohmed K. , Jabbehdari Sayena , Neuhouser Adam , Siddiqui Mohammed Z. , Yang Yit C. , Sallam Ahmed B.
Published: October 2021

Purpose:

To compare the visual outcomes and the rate of intraoperative complications in eyes with and without retinal vein occlusion (RVO) after phacoemulsification over a period of 15 years in a real-world clinical setting.

Setting:

8 independent U.K. National Health Service ophthalmology departments.

Design:

Retrospective, multicenter cohort study.

Methods:

Eyes were classified based on the presence or absence of RVO. For analyzing visual acuity (VA) and the incidence of postoperative cystoid macular edema, eyes with any copathology, combined ocular surgical procedures, and intraoperative complications, or of diabetic patients were excluded.

Results:

Of 178 856 eyes, 1796 eyes with RVO preoperatively and 177 060 eyes without RVO were allocated to the RVO group and the reference group, respectively. Cataract surgery in eyes with RVO was associated with an improvement in the mean VA of 0.35 logMAR (3 to 4 Snellen lines), and a substantial gain (≥0.30 logMAR units [3 Snellen lines]) was achieved in 55.10% of eyes at 4 to 12 weeks postoperatively. The mean postoperative VA was worse in eyes with RVO compared with that in eyes without RVO at 4 to 12 weeks (logMAR 0.40 vs 0.12 [20/50 vs 20/25]; P < .0001). The proportion of eyes achieving a visual gain of ≥ 0.3 logMAR (3 Snellen lines) was also lower in eyes with RVO (55.10% vs 64.55%; P = .0076). There was no statistically significant difference in posterior capsule rupture rates between the 2 groups (1.73% vs 1.72%; P = .9741).

Conclusions:

Although postoperative vision improved significantly in eyes with RVO after cataract surgery, this improvement was worse than that achieved by eyes without RVO.
Dimensions of the limbus–ciliary sulcus region by OCT and correlation study in a large population
Authors: Fernández-Vigo José Ignacio , Shi Hang , Almorín-Fernández-Vigo Ignacio , Burgos-Blasco Bárbara , De-Pablo-Gómez-de-Liaño Lucía , Kudsieh Bachar , Fernández-Vigo José Ángel , Macarro-Merino Ana
Published: October 2021

Purpose:

To assess the dimensions of the limbus–ciliary sulcus region measured by swept-source optical coherence tomography (SS-OCT) and conduct a correlation study in a large healthy population.

Setting:

Centro Internacional de Oftalmología Avanzada, Madrid, Spain.

Design:

Cross-sectional study.

Methods:

The dimensions of the limbus–ciliary sulcus region were measured in the temporal and nasal quadrants using a SS-OCT. The limbus–sulcus distance (LSD), the posterior iris line-ocular surface to limbus distance (PIOLD), and the angle-to-sulcus distance (ASD) were measured. These distances were then assessed for correlations with factors such as age, sex, refractive error, anterior chamber angle (ACA), ciliary muscle thickness (CMT), conjunctival–Tenon capsule thickness (CTT), and anterior scleral thickness (AST).

Results:

The mean age of the participants was 41.0 ± 18.2 years (range 5 to 86) and the mean refractive error −0.75 ± 3.3 diopters (range −10 to 7). The LSD could be measured in 93.2% of the participants (625 eyes out of 670 eyes), with a mean of 1.35 ± 0.12 mm (range 0.96 to 1.75) and 1.33 ± 0.12 mm (range 1.05 to 1.68) in the temporal and nasal quadrants, respectively, and a correlation of R = 0.616 (P < .001) between them. PIOLD measured 2.22 ± 0.31 mm (1.42 to 2.98), and ASD was 0.21 ± 0.05 mm (0.01 to 0.40). No correlation was observed between LSD with age, spherical error, sex, or ACA (P ≥ .247). However, LSD exhibited the highest correlation with AST (R = 0.466), followed by CTT (R = 0.309) and CMT (R = 0.259).

Conclusions:

The SS-OCT allowed for an accurate in vivo measurement of the dimensions of the limbus–ciliary sulcus region.
Nutritional supplementation to enhance the efficacy of exercise training in older adults: what is the evidence from the latest randomized controlled trials?
Authors: Verdijk Lex B.
Published: October 2021

Purpose of review

This review summarizes recent studies that assessed whether nutritional supplementation enhances the efficacy of exercise training in older adults, focusing on the benefits for physical/functional performance of protein, vitamin D, or multi-ingredient supplementation.

Recent findings

Studies applying long-term exercise training strongly support the benefits of different exercise regimens for muscle strength and function but most studies do not provide direct evidence for protein, vitamin D, or multi-ingredient supplementation to further augment such improvements in older adults. Several methodological limitations are addressed that likely limited the reliability to convincingly establish or refute any additive effects of supplementation. Only when specifically tailored to the population under study, ensuring proper intensity, duration, and adherence to exercise, and aiming for a daily intake of ∼1.5 g protein per kg body mass, and ∼800 IU of vitamin D supplementation, there appears to be some potential to augment the efficacy of long-term exercise training in older adults, with potentially greater benefits in compromised older subpopulations.

There is some support for the efficacy of nutritional supplementation to further augment the beneficial effects of prolonged exercise training in older adults but any intervention needs tailoring of both the exercise and the nutritional intervention towards the intended (sub)population.
Can specific nutrients, foods, or dietary patterns modulate cognitive function in (older) adults? Latest evidence from randomized controlled trials
Authors: Ros Emilio
Published: October 2021

Purpose of review

Epidemiological findings and results of randomized clinical trials in the last two decades have identified diet as a modifiable risk factor for cognitive decline, a predementia stage that is increasing worldwide as population ages. The literature on this critical association is expanding, making this review relevant and timely.

Recent findings

Data from 15 trials and several systematic reviews/meta-analyses indicate that, in healthy older adults, isolated nutrients or antioxidant-rich foods usually fail to improve cognition. However, studies targeting populations at risk of cognitive decline tend to have positive results. There is ample epidemiological evidence of cognitive benefit from plant-based dietary patterns (i.e., Mediterranean diet), but more clinical trials are needed. Long-term multicomponent trials, simultaneously targeting several risk factors in patients with early dementia stages, offer promising evidence. A long-term multinutrient intervention in patients at risk for dementia appears as a sound preventive strategy.

This review summarizes the latest evidence on nutrients, foods, and dietary patterns as tools to improve cognition and promote brain health. Dietary changes are important to help delay cognitive decline, particularly in populations more at risk. Large-scale strategies based on healthy diets combined with other health-promoting lifestyle changes should be a public health priority.
The Association of Childhood Maltreatment, Sex, and Hair Cortisol Concentrations With Trajectories of Depressive and Anxious Symptoms Among Adult Psychiatric Inpatients
Authors: Cantave Christina Y. , Ouellet-Morin Isabelle , Giguère Charles-Édouard , Lupien Sonia J. , Juster Robert-Paul , Geoffrion Steve , Marin Marie-France
Published: October 2021

Objective

Depression and anxiety symptoms are commonly observed among clinical populations, especially among women and maltreated individuals. Few investigations have, however, assessed the existence of distinct symptoms trajectories among clinical populations and how these relate to childhood maltreatment, sex differences, and stress physiology indexed by hair cortisol concentrations (HCCs). The current study a) identified distinct depression and anxious trajectories in a sample of psychiatric inpatients followed up prospectively from their admission to a psychiatric emergency service, and b) examined whether HCC, childhood maltreatment, and sex independently and jointly predict these trajectories.

Methods

Adult inpatients (n = 402; 55% women) were recruited upon admission to psychiatric emergency service (T1) during which HCC (reflecting cortisol secretion for the last 3 months), childhood maltreatment, and depression and anxiety symptoms were assessed. Symptoms were reevaluated when patients were discharged from the hospital (T2), admitted to outpatient clinics (T3), and 12 months later or at the end of outpatient treatment (T4).

Results

Three trajectories were identified for depression and anxiety symptoms. Among men, higher HCC predicted higher odds of evincing chronic depressive symptoms compared with a low stable trajectory (odds ratio [OR] = 3.46, 95% confidence interval [CI] = 1.43–8.40). Greater childhood maltreatment among men predicted higher chances of exhibiting chronic anxious symptoms than the low stable (OR = 1.47, 95% CI = 1.07–2.02) and the high decreasing trajectories (OR = 0.70, 95% CI = 0.51–0.95). Opposite findings were noted for women.

Conclusions

Childhood maltreatment and HCC should be further investigated as predictors of anxious and depressive trajectories, during which sex-specific associations ought to be considered.
COVID-19 Vaccination Manifesting as Unilateral Lymphadenopathies Detected by 18F-Choline PET/CT
Authors: Albano Domenico , Volpi Giulia , Dondi Francesco , Giubbini Raffaele , Bertagna Francesco
Published: October 2021

A 79-year-old man with a history of prostate adenocarcinoma treated with prostatectomy underwent 18F-FCH PET/CT for restaging purpose, which was negative for relapse but showed the presence of choline-positive lymph nodes in the left axilla. The patient underwent a COVID-19 vaccination in the left arm 6 days prior. Thus, PET/CT findings were considered as inflammatory lymph nodes. With the current drive of global COVID-19 immunization, this case underlines the importance of knowing vaccination history to interpret correctly the findings and to avoid false-positive reports.
Conservative Management of Severe Medication-Related Osteonecrosis of the Jaw With Pathological Fracture
Authors: Varidel Alistair , Wong Eva
Published: October 2021

Medication-related osteonecrosis of the jaw (MRONJ) is a well-known risk following dental extraction in patients taking certain medications. Pathological fracture secondary to MRONJ often requires complex operative intervention.

This case demonstrates the conservative management of pathological fracture secondary to MRONJ in a patient with multiple comorbidities. The patient developed MRONJ with pathological fracture following extraction of the mandibular second molar. The patient presented with significant surgical risk factors, having hypertension and a recent stroke, causing dense left hemiparesis, subsequently resulting in transition to high-level nursing care. Given the high risk of reconstructive surgery, nonoperative management was undertaken. Following a course of long-term antibiotics with resolution of signs of infection, the case was managed conservatively with chlorhexidine-based mouthwash and soft diet.

With routine clinico-radiographic assessment and optimal oral health care, the pathological fracture did not require operative intervention. Healing progressed well with no clinical complications and radiographic evidence of good healing at 6- and 12-month follow-up on orthopantomogram.

A role for conservative management of pathological fractures secondary to MRONJ yet exists, especially in the elderly population. This case highlights the importance of developing treatment plans based on individual patient context and clinical assessment.
Hardship and Humanity: A Closer Qualitative Look at Surgical Training and Its Effects on Trainees From the Perspectives of Loved Ones
Authors: Kemp Michael T. , Evans Julie , Rivard Samantha J. , Sharma Sriganesh B. , Williams Aaron M. , Coleman Dawn M. , Dimick Justin , Sandhu Gurjit
Published: October 2021

Objective:

The aim of this study was to obtain novel perspectives regarding the effects that surgical training has on the well-being of trainees.

Summary Background Data:

Improving trainee well-being is a national concern given high rates of burnout, depression, and suicide among physicians. Supporters of surgical trainees may offer new perspectives regarding the effects of surgical training and point to strategies to optimize trainee wellness.

Methods:

This qualitative study employs semi-structured interviews of 32 support persons of trainees at a single tertiary care center with multiple surgical training programs. Interviews focused on perspectives related to supporting a surgical trainee. Interview transcripts underwent qualitative analysis with semantic and conceptual coding. Themes related to effects of training on trainee wellness are reported.

Results:

Four themes were identified: Who Can Endure the Most Hardship?—trainee attributes and programmatic factors contribute to trainees feeling the need to constantly endure the most hardship; Consequences of Hardship—constantly enduring hardships has significant negative effects on wellness; Trainees are Humans—trainees are people with basic human needs, especially the need for worth; Research Time as Refuge—dedicated research time is treated as an oasis away from clinical hardships.

Conclusions:

Perspectives from support persons can offer valuable insight into the wellness needs of surgical trainees. According to support persons, surgical training profoundly negatively impacts trainee wellness. Unlike during clinical training, dedicated research time is a period during which wellness can be prioritized. Programs should provide greater attention to mitigating the negative ramifications of surgical training and promoting wellness in a longitudinal fashion throughout training.
Radical Minimally Invasive Surgery After Immuno-chemotherapy in Initially-unresectable Stage IIIB Non-small cell Lung Cancer
Authors: Deng Hongsheng , Liu Jun , Cai Xiuyu , Chen Jiawei , Rocco Gaetano , Petersen René Horsleben , Brunelli Alessandro , Ng Calvin S. H. , D’Amico Thomas A. , Liang Wenhua , He Jianxing
Published: October 2021

Introduction:

Use of neoadjuvant immunotherapy agent in advanced stage NSCLC is controversial. Herein, we aim to report on a case series of successful conversion from initial unresectable stage cIIIB NSCLC to radical minimally invasive surgery through immunochemotherapy; with particular attention given to surgical outcomes and survival benefit of surgery.

Methods:

Fifty-one patients with initial stage cIIIB NSCLC who received PD-1 agents plus platinum-based chemotherapy between May, 2018 to August, 2020 were retrospectively identified. Surgical and oncological outcomes of enrolled patients were collected.

Results:

Of 31 patients who underwent subsequent resection, 23 (74.2%) patients underwent lobectomy, 1 (3.2%) underwent pneumonectomy, 5 (16.1%) underwent sleeve lobectomy, and 2 (6.5%) with bilobectomy. The median surgical time was 205 minutes (range, 100–520). The average blood loss was 185 (range: 10–1100) ml. Dense adhesions or fibrosis was noted in 15 cases. The median postoperative hospital stay was 6 (range: 3–13) days. No surgical-related mortality was recorded, only 5 patients (16.1%) experienced any postoperative morbidity (no grade 3 complications). Ten patients (32.3%) had major pathological response, with mediastinal down-staging been observed in 22/31 (71.0%) patients. With a median after up of 15.4 months, thirty-one patients that had surgery had relatively longer median DFS/PFS compared to that of either non-responders or responders that without surgery (27.5 vs. 4.7 vs. 16.7 months, respectively).

Conclusions:

Radical surgery after chemoimmunotherapy in initial unresectable stage IIIB NSCLC seems to be safe with low surgical-related mortality and morbidity, and was favorably associated with longer DFS/PFS compared to those without surgery.
Flavobacterium dauae sp. nov., isolated from rhizosphere soil of a tomato plant
Authors: Jung Eun Joo , Choi Soo Yeon , Lee Sang-Moo , Song Ju Yeon , Lee Hyoung Ju , Kim Eunjin , Lee Pyeong An , Choi Kihyuck , Kim Jihyun F. , Lee Seon-Woo
Published: October 2021

A bacterial strain, designated TCH3-2T, was isolated from the rhizosphere of tomato plant grown at Dong-A University Agricultural Experiment Station, Republic of Korea. The strain was Gram-stain-negative, obligate aerobic, orange yellow-coloured, motile by gliding and short rod-shaped. Strain TCH3-2 T only grew on 1/2 tryptic soy agar and Luria–Bertani agar among the media tested, with optimum growth at 28 °C and pH 7. Salt of 1 % NaCl was necessary to support the growth of TCH3-2T. Strain TCH3-2T produced flexirubin-type pigments. The predominant cellular fatty acids were iso-C15 : 0 (55.6 %), iso-C17 : 0 3-OH (17.9 %), summed feature 9 (comprising C16 : 0 10-methyl and/or iso-C17 : 1
 ω9c; 10.5 %), iso-C15 : 0 3-OH (4.8 %) and anteiso-C15 : 0 (2.3 %). The major menaquinone was menaquinone-6 and the major polar lipids were phosphatidylethanolamine, five unknown aminolipids and three unknown lipids. Phylogenetic analysis based on 16S rRNA sequences indicated that TCH3-2T was closely related to

Flavobacterium ummariense

DS-12T (95.16 %),

Flavobacterium marinum

SW105T (95.14 %) and

Flavobacterium viscosus

YIM 102796T (94.54 %). The draft genome of TCH3-2T comprised ca. 2.8 Mb with a G+C content of 34.61 mol%. The average nucleotide identity and digital DNA–DNA hybridization values between TCH3-2T and closely related

Flavobacterium

species showed that it belongs to a distinct species. Furthermore, the results of morphological, physiological and biochemical tests allowed further phenotypic differentiation of TCH3-2T from its closest relatives. Thus, chemotaxonomic characteristics together with phylogenetic affiliation illustrate that TCH3-2T represents a novel species of the genus

Flavobacterium

, for which the name Flavobacterium dauae sp. nov. (type strain TCH3-2T=KACC 19054T=JCM 34025T) is proposed.
Pseudooceanicola endophyticus sp. nov., a novel endophytic bacterium isolated from bark Aegiceras corniculatum
Authors: Zheng Zhou-Qing , Chen Ming-Sheng , Yan Xiao-Rui , Tuo Li
Published: October 2021

A Gram-stain-negative, aerobic, short-rod-shaped bacterium, designated strain CBS1P-1T, was isolated from a surface-sterilized bark of Aegiceras corniculatum. Growth of strain CBS1P-1T was observed with between 0 and 12.0 % (w/v) NaCl (optimally with 5.0 %) and at between pH 6.0–9.0. It grew at temperatures between 25–37 °C (optimum, 30 °C). Chemotaxonomic analysis showed that ubiquinone-10 was the respiratory quinone. The lipids comprised diphosphatidylglycerol, phosphatidylglycerol, an unidentified glycolipid, an unidentified phospholipid and an unidentified aminolipid. The major fatty acids of strain CBS1P-1T were C18 : 1
 ω7c, C16 : 0 and C19 : 0 cyclo ω8c. Phylogenetic analyses based on 16S rRNA gene sequences showed that strain CBS1P-1T was most related to

Pseudooceanicola antarcticus

CGMCC 1.12662T with a sequence similarity of 96.5 %. The average nucleotide identity and digital DNA–DNA hybridization values between strain CBS1P-1T and

P. antarcticus

1.12662T were 77.5 and 21.1 %, respectively. The G+C content of the genomic DNA was 67.3 mol%. Based on phylogenetic, chemotaxonomic and phenotypic data, strain CBS1P-1T is considered to represent a novel species of the genus

Pseudooceanicola

, for which the name Pseudooceanicola endophyticus is proposed. The type strain is CBS1P-1T (=KCTC 62836T=CGMCC 1.13743T).
Dynamics of deep water and N uptake under varied N and water supply
Authors: Chen Guanying , Rasmussen Camilla Ruø , Dresbøll Dorte Bodin , Smith Abraham George , Thorup-Kristensen Kristian
Published: October 2021

Aims

Enhanced nitrogen (N) and water uptake from deep soil layers may increase resource use efficiency whilst maintaining yield under stressed conditions. Winter oilseed rape (Brassica napusL.) can develop deep roots and access deep-stored resources such as N and water, while this potential has large uncertainties in variable environments. In this study, we aimed to evaluate the effects of reduced N and water supply on deep N and water uptake.

Methods

Oilseed rape plants grown in outdoor rhizotrons were supplied with 240 and 80 kg N ha-1respectively in 2019 whereas a well-watered and a water-deficit treatment were established in 2020. To track deep water and N uptake, a mixture of2H2O and Ca(15NO3)2was injected into the soil column at 0.5 and 1.7 m depths. δ2H in transpiration water and δ15N in leaves were measured after injection. δ15N in biomass samples were also measured.

Results

Differences in N or water supply had little effect on root growth. The low N treatment reduced water uptake throughout the soil profile, but caused a non-significant increment in15N uptake efficiency at both 0.5 and 1.7 m. Water deficit in the upper soil layers led to compensatory deep water, while N uptake was not altered by soil water status.

Conclusion

Our findings demonstrate that for winter oilseed rape, high N application and water deficiency in shallow layers increases deep water uptake, and that the efficiency of deep N uptake is mainly sensitive to N supply rather than water supply.
Clonal hematopoiesis is associated with increased toxicity in large B-cell lymphoma patients treated with chimeric antigen receptor T cell therapy
Authors: Saini Neeraj Y. , Swoboda David M. , Greenbaum Uri , Ma Jungsheng , Patel Romil , Devashish Kartik , Das Kaberi , Tanner Mark R. , Strati Paolo , Nair Ranjit , Fayad Luis E. , Ahmed Sairah , Lee Hun Ju , Iyer Swaminathan , Steiner Raphael , Jain Nitin , Nastoupil Loretta , Loghavi Sanam , Tang Guilin , Jain Preetesh , Wang Michael , Westin Jason , Green Michael R. , Sallman David , Padron Eric , Davila Marco , Locke Frederick L. , Champlin Richard , Shpall Elizabeth , Kebriaei Partow , Flowers Christopher R. , Jain Michael , Wang Feng , Futreal Andrew , Gillis Nancy , Neelapu Sattva S. , Takahashi Koichi
Published: October 2021

To explore the role of clonal hematopoiesis (CH) on chimeric antigen receptor (CAR) T-cell therapy outcomes, we performed targeted deep-sequencing on 114 large B-cell lymphoma patients treated with anti-CD19 CAR T-cells. We detected CH in 42 (36.8%) pre-treatment patient samples, most frequently in PPM1D (19/114) and TP53 (13/114) genes. The incidence of grade ≥3 immune-effector cell-associated neurotoxicity syndrome (ICANS) was higher in CH-positive patients compared to CH-negative patients (45.2% vs. 25.0%, p=0.038). Higher toxicities with CH were primarily driven by three CH genes, DNMT3A, TET2 and ASXL1 (DTA mutations). The incidence of grade ≥3 ICANS [58.9% vs. 25%, p=0.02] and grade ≥3 cytokine release syndrome [17.7% vs. 4.2%, p=0.08] were higher in patients with DTA mutations than those without CH. The estimated 24-month cumulative incidence of therapy-related myeloid neoplasms after CAR-T therapy was higher in patients with CH than those without CH (19% [95%CI: 5.5-38.7] vs. 4.2% [95%CI: 0.3-18.4], p=0.028).

Statement of Significance

Our study reveals that clonal hematopoiesis mutations, especially those associated with inflammation (DNMT3A, TET2, ASXL1), are associated with severe grade toxicities in lymphoma patients receiving anti-CD19 chimeric antigen receptor therapy. Further studies to investigate the mechanisms and interventions to improve toxicities in the context of CH are warranted.
Occlusion of lip movements impairs reconstruction of acoustic speech features and higher-level segmentational features in the presence of a distractor speaker
Authors: Haider Chandra Leon , Suess Nina , Hauswald Anne , Park Hyojin , Weisz Nathan
Published: October 2021

Multisensory integration enables stimulus representation even when the sensory input in a single modality is weak. In the context of speech, when confronted with a degraded acoustic signal, congruent visual inputs promote comprehension. When this input is occluded speech comprehension consequently becomes more difficult. But it still remains inconclusive which levels of speech processing are affected under which circumstances by occlusion of the mouth area. To answer this question, we conducted an audiovisual (AV) multi-speaker experiment using naturalistic speech. In half of the trials, the target speaker wore a (surgical) face mask, while we measured the brain activity of normal hearing participants via magnetoencephalography (MEG). We additionally added a distractor speaker in half of the trials in order to create an ecologic difficult listening situation. A decoding model on the clear AV speech was trained and used to reconstruct crucial speech features in each condition. We found significant main effects of face masks on the reconstruction of acoustic features, such as the speech envelope and spectral speech features (i.e. pitch and formant frequencies), while reconstruction of higher level features of speech segmentation (phoneme and word onsets) were especially impaired through masks in difficult listening situations. As we used surgical face masks in our study, which only show mild effects on speech acoustics, we interpret our findings as the result of the occluded lip movements. This idea is in line with recent research showing that visual cortical regions track spectral modulations. Our findings extend previous behavioural results, by demonstrating the complex contextual effects of occluding relevant visual information on speech processing.

Highlights

Surgical face masks impair neural tracking of speech features

Tracking of acoustic features is generally impaired, while higher level segmentational features show their effects especially in challenging listening situations

An explanation is the prevention of a visuo-phonological transformation contributing to audiovisual multisensory integration
Prediction of Inefficient BCI Users based on Cognitive Skills and Personality Traits
Authors: Hagedorn Laura J. , Leeuwis Nikki , Alimardani Maryam
Published: October 2021

BCI inefficiency is one of the major challenges of motor imagery brain-computer interfaces (MI-BCI). Past research suggests that certain cognitive skills and personality traits correlate with MI-BCI real-time performance. Other studies have examined sensorimotor rhythm changes (also known as μ suppression) as a valuable indicator of successful execution of the MI task. This research aims to combine these insights by investigating whether cognitive factors and personality traits can make predictions of a user’s ability to modulate μ rhythms during a MI-BCI task. Data containing 55 subjects who completed a MI task was employed, and a stepwise linear regression model was implemented to select the most relevant features for μ suppression prediction. The most accurate model was based on these factors: Spatial Ability, Visuospatial Memory, Autonomy, and Vividness of Visual Imagery. Further correlation analyses showed that a novice user’s μ suppression during a MI-BCI task can be predicted based on their visuospatial memory ability, as measured by the Design Organization Test (DOT).
Biotechnology data analysis training with Jupyter Notebooks
Authors: Liebal Ulf W. , Schimassek Rafael , Broderius Iris , Maaßen Nicole , Vogelgesang Alina , Weyers Philipp , Blank Lars M.
Published: October 2021

Biotechnology has experienced innovations in analytics and data processing. As the volume of data and its complexity grows, new computational procedures for extracting information are developed. However, the rate of change outpaces the adaptation of biotechnology curricula, necessitating new teaching methodologies to equip biotechnologists with data analysis abilities. To simulate experimental data, we created a virtual organism simulator (silvio) by combining diverse cellular and sub-cellular microbial models. silvio was utilized to construct a computer-based instructional workflow with important steps during strain characterization and recombinant protein expression. The instructional workflow is provided as a Jupyter Notebook with comprehensive explanatory text of biotechnological facts and experiment simulations using silvio tools. The students conduct data analysis in Python or Excel. This instructional workflow was separately implemented in two distance courses for Master’s students in biology and biotechnology. The concept of using virtual organism simulations that generate coherent results across different experiments can be used to construct consistent and motivating case studies for biotechnological data literacy.
Fast Optoacoustic Mesoscopy of Microvascular Endothelial Dysfunction in Cardiovascular Risk and Disease
Authors: He Hailong , Karlas Angelos , Fasoula Nikolina-Alexia , Kallmayer Michael , Aguirre Juan , Eckstein Hans-Henning , Ntziachristos Vasilis
Published: October 2021

Microvascular endothelial dysfunction (ED) precedes the ED in larger arteries and is an early marker of cardiovascular disease (CVD). While precise assessment of microvascular ED could thus be used for the early detection and risk stratification of CVD, detailed interrogation of skin microvascular ED is limited by the technology available. Herein, we applied a novel approach for the non-invasive assessment of skin microvascular ED by developing fast plane raster-scan optoacoustic mesoscopy (FP-RSOM) to visualize and quantify skin microvasculature perfusion changes during post-occlusive hyperemia (PORH) tests. We combined static three-dimensional RSOM imaging with fast dynamic FP-RSOM measurements (1 frame / second) in human skin in vivo, which allowed for the first time to fully visualize the cutaneous microvascular response and further quantify changes of individual vessel diameter, total blood volume and vessel density during the PORH process. We further computed biomarkers from FP-RSOM images to quantify skin endothelial function within different skin layers as a function of skin depth, while conventional approaches mainly measure overall changes within sampled tissue volumes. FP-RSOM applied on smokers and patients with CVD showed clear ED in both groups compared to healthy volunteers. Moreover, FP-RSOM imaging showed higher sensitivity in quantifying the effects of smoking and CVD on skin microvascular endothelial function compared to clinically used laser Doppler flowmetry and tissue spectrometry (O2C). Our study introduces FP-RSOM as a novel tool to visualize and quantify skin microvascular ED as an early marker for the diagnostics and monitoring of cardiovascular risk and disease.
Light regulated SIK1 remodels the synaptic phosphoproteome to induce sleep
Authors: Taylor Lewis , Palumaa Teele , Reardon Paul K , Walsh Steven , Johnson Bradley H , Liberatori Sabrina , Hasan Sibah , Clark Kristopher , Cohen Philip , Vasudevan Sridhar , Peirson Stuart , Mohammed Shabaz , Vyazovskiy Vladyslav , Foster Russell G , Jagannath Aarti
Published: October 2021

The sleep and circadian systems act in concert to regulate sleep-wake timing, yet the molecular mechanisms that underpin their interaction to induce sleep remain unknown. Synaptic protein phosphorylation, driven by the kinase SIK3, correlates with sleep pressure, however it is unclear whether these phosphoproteome changes are causally responsible for inducing sleep. Here we show that the light-dependent activity of SIK1 controls the phosphorylation of a subset of the brain phosphoproteome to induce sleep in a manner that is independent of sleep pressure. By uncoupling phosphorylation and sleep induction from sleep pressure, we establish that synaptic protein phosphorylation provides a causal mechanism for the induction of sleep under different environmental contexts. Furthermore, we propose a framework that details how the salt-inducible kinases regulate the synaptic phosphoproteome to integrate exogenous and endogenous stimuli, thereby providing the molecular basis upon which the sleep and circadian systems interact to control the sleep-wake cycle.
A yeast with muscle doesn’t run faster: full humanization of the glycolytic pathway in Saccharomyces cerevisiae
Authors: Boonekamp Francine J. , Knibbe Ewout , Vieira-Lara Marcel A. , Wijsman Melanie , Luttik Marijke A.H. , van Eunen Karen , den Ridder Maxime , Bron Reinier , Almonacid Suarez Ana Maria , van Rijn Patrick , Wolters Justina C. , Pabst Martin , Daran Jean-Marc , Bakker Barbara , Daran-Lapujade Pascale
Published: October 2021

While transplantation of single genes in yeast plays a key role in elucidating gene functionality in metazoans, technical challenges hamper the humanization of full pathways and processes. Empowered by advances in synthetic biology, this study demonstrates the feasibility and implementation of full humanization of glycolysis in yeast. Single gene and full pathway transplantation revealed the remarkable conservation of both glycolytic and moonlighting functions and, combined with evolutionary strategies, brought to light novel, context-dependent responses. Remarkably, human hexokinase 1 and 2, but not 4, required mutations in their catalytic or allosteric sites for functionality in yeast, while hexokinase 3 was unable to complement its yeast ortholog. Comparison with human tissues cultures showed the preservation of turnover numbers of human glycolytic enzymes in yeast and human cell cultures. This demonstration of transplantation of an entire, essential pathway paves the way to the establishment of species, tissue and disease-specific metazoan models.

One Sentence Summary

This work demonstrates the successful humanization of an entire pathway in Saccharomyces cerevisiae and establishes an attractive strategy to study (human) glycolysis architecture and regulation.

Highlights

The successful humanization of the entire glycolytic pathway in yeast offers new microbial models for both fundamental and applied studies.

Both glycolytic and moonlighting functions and turnover numbers of glycolytic enzymes are highly conserved between yeast and human.

Functionality of human hexokinases 1 and 2 in yeast requires mutations in the catalytic or allosteric binding sites.

Combination of single gene and full transplantation with laboratory evolution reveals context-dependent activity and evolution of glycolytic enzymes.
Neurofibromin 1 controls metabolic balance and Notch-dependent quiescence of juvenile myogenic progenitors
Authors: Wei Xiaoyan , Lienhard Matthias , Murgai Arunima , Franke Julia , Pöhle-Kronawitter Sophie , Kotsaris Georgios , Wu Hao , Börno Stefan , Timmermann Bernd , Glauben Rainer , Stricker Sigmar
Published: October 2021

Patients affected by neurofibromatosis type 1 (NF1) frequently show muscle weakness with unknown etiology. Here we show that Neurofibromin-1 (Nf1) is not required in muscle fibers, but specifically in early postnatal myogenic progenitors (MPs), where Nf1 loss led to cell cycle exit and differentiation blockade, depleting the MP pool resulting in reduced myonuclear accrual as well as reduced muscle stem cell numbers. This was caused by precocious induction of stem cell quiescence coupled to metabolic reprogramming of MPs impinging on glycolytic shutdown, which was conserved in muscle fibers. We show that a Mek/Erk/NOS pathway hypersensitizes Nf1-deficient MPs to Notch signaling, consequently, early postnatal Notch pathway inhibition ameliorated premature quiescence, metabolic reprogramming and muscle growth. This reveals an unexpected role of Ras/Mek/Erk signaling supporting postnatal MP quiescence in concert with Notch signaling, which is controlled by Nf1 safeguarding coordinated muscle growth and muscle stem cell pool establishment. Furthermore, our data suggest transmission of metabolic reprogramming across cellular differentiation, affecting fiber metabolism and function in NF1.
Metrics of High Cofluctuation and Entropy to Describe Control of Cardiac Function in the Stellate Ganglion
Authors: Gurel Nil Z. , Sudarshan Koustubh B. , Hadaya Joseph , Karavos Alex , Temma Taro , Hori Yuichi , Armour J. Andrew , Kember Guy , Ajijola Olujimi A.
Published: October 2021

Stellate ganglia within the intrathoracic cardiac control system receive and integrate central, peripheral, and cardiopulmonary information to produce postganglionic cardiac sympathetic inputs. Pathological anatomical and structural remodeling occurs within the neurons of the stellate ganglion (SG) in the setting of heart failure. A large proportion of SG neurons function as interneurons whose networking capabilities are largely unknown. Current therapies are limited to targeting sympathetic activity at the cardiac level or surgical interventions such as stellectomy, to treat heart failure. Future therapies that target the stellate ganglion will require understanding of their networking capabilities to modify any pathological remodeling. We observe SG networking by examining cofluctuation and specificity of SG networked activity to cardiac cycle phases. We investigate network processing of cardiopulmonary transduction by SG neuronal populations in porcine with chronic pacing-induced heart failure and control subjects during extended in-vivo extracellular microelectrode recordings. We find that information processing and cardiac control in chronic heart failure by the SG, relative to controls, exhibits: i) more frequent, short-lived, high magnitude cofluctuations, ii) greater variation in neural specificity to cardiac cycles, and iii) neural network activity and cardiac control linkage that depends on disease state and cofluctuation magnitude.
Radical pairs may play a role in microtubule reorganization
Authors: Zadeh-Haghighi Hadi , Simon Christoph
Published: October 2021

The exact mechanism behind general anesthesia remains an open question in neuroscience. It has been proposed that anesthetics selectively prevent consciousness and memory via acting on microtubules (MTs). It is known that the magnetic field modulates MT organization. A recent study shows that a radical pair model can explain the isotope effect in xenon-induced anesthesia and predicts magnetic field effects on anesthetic potency. Further, reactive oxygen species are also implicated in MT stability and anesthesia. Based on a simple radical pair mechanism model and a simple mathematical model of MT organization, we show that magnetic fields can modulate spin dynamics of naturally occurring radical pairs in MT. We show that the spin dynamics influence a rate in the reaction cycle, which translates into a change in the MT density. We can reproduce magnetic field effects on the MT concentration that have been observed. Our model also predicts additional effects at slightly higher fields. Our model further predicts that the effect of zinc on the MT density exhibits isotopic dependence. The findings of this work make a connection between microtubule-based and radical pair-based quantum theories of consciousness.
Evaluating the reliability, validity, and utility of overlapping networks: Implications for network theories of cognition
Authors: Cookson Savannah L. , D’Esposito Mark
Published: October 2021

Brain network definitions typically assume non- or minimal overlap, ignoring regions’ connections to multiple networks. However, new methods are emerging that emphasize network overlap. Here, we investigated the reliability and validity of one assignment method, the mixed membership algorithm, and explored its potential utility for identifying gaps in existing network models of cognition. We first assessed between-sample reliability of overlapping assignment with a split-half design; a bootstrapped Dice similarity analysis demonstrated good agreement between the networks from the two subgroups. Next, we assessed whether overlapping networks captured expected nonoverlapping topographies; overlapping networks captured portions of one to three nonoverlapping topographies, which aligned with canonical network definitions. Following this, a relative entropy analysis showed that a majority of regions participated in more than one network, as is seen biologically, and many regions did not show preferential connection to any one network. Finally, we explored overlapping network membership in regions of the Dual-Networks model of cognitive control, showing that almost every region was a member of multiple networks. Thus, the mixed membership algorithm produces consistent and biologically plausible networks, which presumably will allow for the development of more complete network models of cognition.