bluuebunny/crossref_metadata_2025 huggingface dataset:
Transcriptome profiling at the transition to the reproductive stage uncovers stage and tissue-specific genes in wheat
Authors: Benaouda Salma , Stöcker Tyll , Schoof Heiko , Léon Jens , Ballvora Agim
Published: January 2023

Background

The transition from vegetative to floral phase is the result of complex crosstalk of exogenous and endogenous floral integrators. This critical physiological event is the response to environmental interaction, which causes biochemical cascades of reactions at different internal tissues, organs, and releases signals that make the plant moves from vegetative status to a reproductive phase. This network controlling flowering time is not deciphered largely in bread wheat. In this study, a comparative transcriptome analysis at a transition time in combination with genetic mapping was used to identify responsible genes in a stage and tissue-specific manner. For this reason, two winter cultivars that have been bred in Germany showing contrasting and stable heading time in different environments were selected for the analysis.

Results

In total, 670 and 1075 differentially expressed genes in the shoot apical meristem and leaf tissue, respectively, could be identified in 23 QTL intervals for the heading date. In the transition apex, Histone methylation H3-K36 and regulation of circadian rhythm are both controlled by the same homoeolog genes mapped in QTL TaHd112, TaHd124, and TaHd137. TaAGL14 gene that identifies the floral meristem was mapped in TaHd054 in the double ridge. In the same stage, the homoeolog located on chromosome 7D of FLOWERING TIME LOCUS T mapped on chr 7B, which evolved an antagonist function and acts as a flowering repressor was uncovered. The wheat orthologue of transcription factor ASYMMETRIC LEAVES 1 (AS1) was identified in the late reproductive stage and was mapped in TaHd102, which is strongly associated with heading date. Deletion of eight nucleotides in the AS1 promoter could be identified in the binding site of the SUPPRESSOR OF CONSTANS OVEREXPRESSION 1 (SOC1) gene in the late flowering cultivar. Both proteins AS1 and SOC1 are inducing flowering time in response to gibberellin biosynthesis.

Conclusion

The global transcriptomic at the transition phase uncovered stage and tissue-specific genes mapped in QTL of heading date in winter wheat. In response to Gibberellin signaling, wheat orthologous transcription factor AS1 is expressed in the late reproductive phase of the floral transition. The locus harboring this gene is the strongest QTL associated with the heading date trait in the German cultivars. Consequently, we conclude that this is another indication of the Gibberellin biosynthesis as the mechanism behind the heading variation in wheat.
Factors related to early readmissions after acute heart failure: a nested case–control study
Authors: Garcia-Gutierrez Susana , Villanueva Ane , Lafuente Iratxe , Rodriguez Ibon , Lozano-Bahamonde Ainara , Murga Nekane , Orus Josefina , Camacho Emilia Rosa , Quintana Jose María , Quiros Raul ,   the ReIC-REDISSEC working group, Onaindia Jose Juan , Fernández-Ruiz Jose , Cacicedo Angela , Escobar Vanessa , Redondo Maximino , Cabello Gloria , Baré Marisa
Published: January 2023

Aims

To describe the main characteristics of patients who were readmitted to hospital within 1 month after an index episode for acute decompensated heart failure (ADHF).

Methods and results

This is a nested case–control study in the ReIC cohort, cases being consecutive patients readmitted after hospitalization for an episode of ADHF and matched controls selected from those who were not readmitted. We collected clinical data and also patient-reported outcome measures, including dyspnea, Minnesota Living with Heart Failure Questionnaire (MLHFQ), Tilburg Frailty Indicator (TFI) and Hospital Anxiety and Depression Scale scores, as well as symptoms during a transition period of 1 month after discharge. We created a multivariable conditional logistic regression model. Despite cases consulted more than controls, there were no statistically significant differences in changes in treatment during this first month. Patients with chronic decompensated heart failure were 2.25 [1.25, 4.05] more likely to be readmitted than de novo patients. Previous diagnosis of arrhythmia and time since diagnosis ≥ 3 years, worsening in dyspnea, and changes in MLWHF and TFI scores were significant in the final model.

Conclusion

We present a model with explanatory variables for readmission in the short term for ADHF. Our study shows that in addition to variables classically related to readmission, there are others related to the presence of residual congestion, quality of life and frailty that are determining factors for readmission for heart failure in the first month after discharge.

Trial Registration: ClinicalTrials.gov Identifier: NCT03300791. First registration: 03/10/2017.
Prevalence and association of frailty with SARS-CoV-2 infection in older adults in Southern Switzerland—Findings from the Corona Immunitas Ticino Study
Authors: Jiang Miao , Corna Laurie , Amati Rebecca , Piumatti Giovanni , Franscella Giovanni , Crivelli Luca , Albanese Emiliano
Published: January 2023

Background

Frailty is an age-associated state of increased vulnerability to stressors that strongly predicts poor health outcomes. Epidemiological evidence on frailty is limited during the COVID-19 pandemic, and whether frailty is associated with the risk of infection is unknown.

Objectives

We derived a robust Frailty Index (FI) to measure the prevalence of frailty and its risk factors in community-dwelling older adults in Southern Switzerland (Ticino), and we explored the association between frailty and serologically confirmed SARS-CoV-2 infection.

Methods

In September 2020, we recruited a random sample of community-dwelling older adults (65 +) in the Corona Immunitas Ticino prospective cohort study (CIT) and assessed a variety of lifestyle and health characteristics. We selected 30 health-related variables, computed the Rockwood FI, and applied standard thresholds for robust (FI < 0.1), pre-frail (0.1 ≤ FI < 0.21), and frail (FI ≥ 0.21).

Results

Complete data for the FI was available for 660 older adults. The FI score ranged between zero (no frailty) and 0.59. The prevalence of frailty and pre-frailty were 10.3% and 48.2% respectively. The log-transformed FI score increased by age similarly in males and females, on average by 2.8% (p < 0.001) per one-year increase in age. Out of 481 participants with a valid serological test, 11.2% were seropositive to either anti-SARS-CoV-2 IgA or IgG. The frailty status and seropositivity were not statistically associated (p = 0.236).

Conclusion

Advanced age increases the risk of frailty. The risk of COVID-19 infection in older adults may not differ by frailty status.
Tracking excess of maternal deaths associated with COVID-19 in Brazil: a nationwide analysis
Authors: Guimarães Raphael Mendonça , Reis Lenice Gnocchi Costa , de Souza Mendes Gomes Maria Auxiliadora , Magluta Cynthia , de Freitas Carlos Machado , Portela Margareth Chrisostomo
Published: January 2023

Background

The COVID-19 pandemic brought a new challenge to maternal mortality in Brazil. Throughout 2020, Brazil registered 549 maternal deaths, mainly in second and third-trimester pregnant women. The objective of this study was to estimate the excess maternal deaths in Brazil caused directly and indirectly by Covid-19 in the year 2020. In addition, we sought to identify clinical, social and health care factors associated with the direct maternal deaths caused by Covid-19.

Methods

We performed nationwide analyses based on data from the Mortality Information System (SIM) for general and maternal deaths and the Influenza Epidemiological Surveillance System (SIVEP-Influenza) for estimates of female and maternal deaths due to COVID-19. Two distinct techniques were adopted. First, we describe maternal deaths directly caused by covid-19 and compare them with the historical series of deaths from covid-19 among women of childbearing age (15 to 49 years). Next, we estimated the total excess maternal mortality. Then, we calculated odds ratios for symptoms, comorbidities, social determination proxies and hospital care aspects between COVID-19 maternal deaths and deaths of women of childbearing age who were not pregnant or no maternal deaths. We chose women of childbearing age (15 to 49 years) as a reference because sex and age introduce differentials in the risk of COVID-19 death.

Results

Most maternal deaths occurred during pregnancy compared to postpartum deaths month by month in 2020 (μ = 59.8%, SD = 14.3%). The excess maternal mortality in 2020 in Brazil was 1.40 (95% CI 1.35–1.46). Even considering excess mortality due to COVID-19 for the childbearing age female population (MMR 1.14; 95% CI 1.13–1.15), maternal mortality exceeded the expected number. The odds of being a black woman, living in a rural area and being hospitalized outside the residence municipality among maternal deaths were 44, 61 and 28% higher than the control group. Odds of hospitalization (OR 4.37; 95% CI 3.39–5.37), ICU admission (OR 1.73; 95% CI 1.50–1.98) and invasive ventilatory support use (OR 1.64; CI 95% 1.42–1.86) among maternal deaths were higher than in the control group.

Conclusions

There was excess maternal mortality in 2020 in Brazil. Even with adjustment for the expected excess mortality from Covid-19 in women of childbearing age, the number of maternal deaths exceeds expectations, suggesting that there were deaths among pregnant and postpartum women indirectly caused by the pandemic, compromising access to prenatal care., adequate childbirth and puerperium.
Ocular and visual perceptive factors associated with treatment outcomes in patients with anisometropic amblyopia
Authors: Hong Jie , Kuo Debbie , Su Han , Li Lei , Guo Yanan , Chu Hang , Fu Jing
Published: January 2023

Background

The aim of this observational study was to identify ocular and visual perceptive risk factors related to treatment results following refractive correction and patching in children with anisometropic amblyopia, who were between the ages of 4 to 14 years old.

Methods

One-hundred and two children with newly diagnosed anisometropic amblyopia were recruited. Successful treatment of amblyopia was defined as the final best corrected visual acuity (BCVA) better than or equal to 0.1 logMAR and amblyopic eye BCVA within 1 line of the sound eye BCVA by the end of the treatment period. BCVA, cycloplegic refraction, stereoacuity, perceptual eye position (PEP) and interocular suppression were measured.

Results

Of these patients, 45.10% achieved successful treatment of amblyopia after refractive correction and patching for 10.5 months. The mean age was not significantly different between patients who were successfully and unsuccessfully treated (5.50 ± 1.59 years vs 6.14 ± 2.19 years, respectively). Patients who failed treatment had significantly larger interocular difference of BCVA at the time of initial treatment (successful group: 0.33 ± 0.29 logMAR, unsuccessful group: 0.65 ± 0.35 logMAR) and after refractive adaptation (successful group: 0.15 ± 0.13 logMAR, unsuccessful group: 0.42 ± 0.35 logMAR). They also had higher spherical equivalent (SE) of amblyopic eyes (successful group: 3.08 ± 3.61 D, unsuccessful group: 5.27 ± 3.38 D), bigger interocular difference of SE (successful group: 0.94 ± 2.71 D, unsuccessful group: 3.09 ± 3.05 D), worse stereoacuity (successful group: 2.32 ± 0.37 log seconds of arc, unsuccessful group: 2.75 ± 0.32 log seconds of arc), larger vertical PEP deviation (successful group: 6.41 ± 6.08 pixel, unsuccessful group: 19.07 ± 24.96 pixel) and deeper interocular suppression (successful group: 21.7 ± 19.7%, unsuccessful group: 37.8 ± 27.1%) than those of successfully treated patients. The most influential treatment failure risk factors were larger vertical PEP deviation [adjusted odds ratio (OR) (95% confidence interval) 1.12 (1.02–1.22)] and worse stereoacuity [adjusted odds ratio (OR) (95% confidence interval) 7.72 (1.50–39.85)] in multiple logistic regression analysis.

Conclusions

Larger vertical PEP deviation and worse stereoacuity were the most influential treatment failure risk factors in children with anisometropic amblyopia. The vertical PEP deviation and stereoacuity, which can reflect interocular interaction, may be useful in predicting the response to therapy.
Factors for incidence risk and prognosis of synchronous brain metastases in pulmonary large cell carcinoma patients: a population-based study
Authors: Zheng Xuan , Mu Shuai , Wang Lijie , Tao Haitao , Huang Di , Huang Ziwei , Li Xiaoyan , Cui Pengfei , Li Tao , Liu Qingyan , Hu Yi
Published: January 2023

Background

Patients with pulmonary large cell carcinoma (LCC) have a high incidence of synchronous brain metastases (SBM) and a poor prognosis. Our study was to evaluate the predictive and prognostic value of the clinical characteristics of pulmonary LCC patients with SBM at initial diagnosis by utilizing the Surveillance, Epidemiology, and End Results (SEER) database.

Methods

LCC patients, diagnosed from 2010 to 2019, were identified from the latest SEER database which was released in April 2022. Logistic regression and Cox regression were used to identify the predictive and prognostic factors for LCC patients with SBM. Propensity score matching (PSM) and Kaplan–Meier analyses were applied to assess different therapy modalities.

Results

A total of 1375 LCC patients were enrolled in this study and 216 (15.7%) of them had SBM at the initial diagnosis. The median overall survival (OS) of LCC patients with SBM was 4 months. Multivariate Cox regression identified age 60–79 (OR 0.57; 95% CI 0.41–0.78; p < 0.001), age ≥ 80 (OR 0.23; 95% CI 0.12–0.45; p < 0.001) and bone metastases (OR 1.75; 95% CI 1.22–2.51; p < 0.001) as significant independent predictors for developing SBM. Multivariable Cox regression revealed that age 60–79, T stage, bone metastases and chemotherapy were independent prognostic factor for OS. The surgery combined with chemotherapy and radiotherapy group, in which all patients were N0 stage and had no other site-specific metastases, exhibited the best median OS of 15 months.

Conclusions

LCC patients with age < 60 or bone metastases were more likely to have SBM at initial diagnosis. Age, T stage, bone metastases and chemotherapy were independent prognostic factors for OS of LCC patients with SBM. Highly selected patients might achieve the best survival benefit from surgery combined with chemotherapy and radiotherapy.
The effect of interactions between BMI and sustained depressive symptoms on knee osteoarthritis over 4 years: data from the osteoarthritis initiative
Authors: Joseph Gabby B. , McCulloch Charles E. , Nevitt Michael C. , Lynch John , Lane Nancy E. , Pedoia Valentina , Majumdar Sharmila , Link Thomas M.
Published: January 2023

Background

To assess the compound effects of BMI and sustained depressive symptoms on changes in knee structure, cartilage composition, and knee pain over 4 years using statistical interaction analyses.

Methods

One thousand eight hundred forty-four individuals from the Osteoarthritis Initiative Database were analyzed at baseline and 4-year follow-up. Individuals were categorized according to their BMI and presence of depressive symptoms (based on the Center for Epidemiological Studies Depression Scale (threshold≥16)) at baseline and 4-year follow-up. 3 T MRI was used to quantify knee cartilage T2over 4 years, while radiographs were used to assess joint space narrowing (JSN). Mixed effects models examined the effect of BMI-depressive symptoms interactions on outcomes of cartilage T2, JSN, and knee pain over 4-years.

Results

The BMI-depressive symptoms interaction was significantly associated with knee pain (p < 0.001) changes over 4 years, but not with changes in cartilage T2(p = 0.27). In women, the BMI-depressive symptoms interaction was significantly associated with JSN (p = 0.01). In a group-based analysis, participants with obesity and depression had significantly greater 4-year changes in knee pain (coeff.(obesity + depression vs. no_obesity + no_depression) = 4.09, 95%CI = 3.60–4.58,p < 0.001), JSN (coeff. = 0.60, 95%CI = 0.44–0.77,p < 0.001), and cartilage T2(coeff. = 1.09, 95%CI = 0.68–1.49,p < 0.001) than participants without depression and normal BMI.

Conclusions

Thecompoundeffects of obesity and depression have greater impact on knee pain and JSN progression compared to what would be expected based on theirindividualeffects.
The choice of endoscopic surgical approach and four steps of operation of inverted papilloma of the maxillary sinus
Authors: Lou Zhengcai
Published: January 2023

Objective

The aim of this study was to determine the long-term efficacy of four steps of operation on the treatment of maxillary sinus (MS) inverted papilloma (IP).

Methods

83 patients who were diagnosed with IP that originated from the MS, underwent four step procedure of attachment sites, including mucosal stripping, periosteum ablation, bone drilling and bone ablation and had postoperative follow-up of 3 years were enrolled.

Results

Of the 83 patients, 59 (71.1%) patients were primary surgery and revision surgery in 24 (28.9%), single attachment was in 31(37.3%) patients and multifocal attachments in 52 (62.7%).When the numbers were not mutually exclusive, the most common origin sites of IPs were the medial wall in 54 (37.2%), lateral wall in 29 (20.0%), anterior wall in 18 (12.4%), inferior wall in 22 (15.2%), posterior in 15 (10.3%), and superior wall in 7 (4.8%). Large MMA alone was performed in 5 (6.0%), MMA combined with medial maxillectomy 76 (91.6%), and MMA combined with Caldwell-Luc approach in 2 (2.4%). No major intra- or postoperative complications were observed. The average follow-up was 41 months (range, 37–61 months). CT and endoscope showed that tumor and symptom recurrence occurred in 2 patients (2.41%). In addition, although the opening of antrostomy was closed and CT revealed the uniform soft tissue shadow and hyperostosis of MS in 11(13.3%) patients, they didn’t report any symptoms and showed well epithelization of middle meatus mucosa.

Conclusion

The four steps of operations of attachment sites of MS IP, including mucosal stripping, periosteum ablation, bone drilling and bone ablation, may effectively prevent the recurrence of MS IP.
Dietary fat induced chylomicron-mediated LPS translocation in a bicameral Caco-2cell model
Authors: Tomassen Monic M. M. , Govers Coen , Vos A. Paul , de Wit Nicole J. W.
Published: January 2023

Background

There is increasing evidence that dietary fat, especially saturated fat, promotes the translocation of lipopolysaccharide (LPS) via chylomicron production in the gut. Chylomicrons can subsequently transport LPS to other parts of the body, where they can induce low-grade chronic inflammation that is linked to various metabolic and gut-related diseases. To identify promising (food) compounds that can prevent or ameliorate LPS-related low-grade inflammation, we developed and optimized a bicameral in vitro model for dietary fat-induced LPS translocation that closely mimics the in vivo situation and facilitates high-throughput screening.

Methods

Caco-2 cells were cultured in monolayers and differentiated to a small intestinal phenotype in 21 days. Thereafter, optimal conditions for fat-induced chylomicron production were determined by apical exposure of Caco-2 cells to a dilution range of in vitro digested palm oil and sunflower oil, optionally preceded by a 1-week apical FBS deprivation (cultured without apical fetal bovine serum). Chylomicron production was assessed by measuring basolateral levels of the chylomicron-related marker apolipoprotein B. Next, LPS was coincubated at various concentrations with the digested oils, and fat-induced LPS translocation to the basolateral side was assessed.

Results

We found that dietary fat-induced LPS translocation in Caco-2 cells was optimal after apical exposure to digested oils at a 1:50 dilution in combination with 750 ng/mL LPS, preceded by 1 week of apical FBS deprivation. Coincubation with the chylomicron blocker Pluronic L81 confirmed that fat-induced LPS translocation is mediated via chylomicron production in this Caco-2 cell model.

Conclusion

We developed a robust Caco-2 cell model for dietary fat-induced LPS translocation that can be used for high-throughput screening of (food) compounds that can reduce LPS-related low-grade inflammation.
LncRNA-TBP mediates TATA-binding protein recruitment to regulate myogenesis and induce slow-twitch myofibers
Authors: Ma Manting , Cai Bolin , Zhou Zhen , Kong Shaofen , Zhang Jing , Xu Haiping , Zhang Xiquan , Nie Qinghua
Published: January 2023

Background

Skeletal muscle is comprised of heterogeneous myofibers that differ in their physiological and metabolic parameters. Of these, slow-twitch (type I; oxidative) myofibers have more myoglobin, more mitochondria, and higher activity of oxidative metabolic enzymes compared to fast-twitch (type II; glycolytic) myofibers.

Methods

In our previous study, we found a novel LncRNA-TBP (for “LncRNA directly binds TBP transcription factor”) is specifically enriched in the soleus (which has a higher proportion of slow myofibers). The primary myoblast cells and animal model were used to assess the biological function of the LncRNA-TBP in vitro or in vivo. Meanwhile, we performed a RNA immunoprecipitation (RIP) and pull-down analysis to validate this interaction between LncRNA-TBP and TBP.

Results

Functional studies demonstrated that LncRNA-TBP inhibits myoblast proliferation but promotes myogenic differentiation in vitro. In vivo, LncRNA-TBP reduces fat deposition, activating slow-twitch muscle phenotype and inducing muscle hypertrophy. Mechanistically, LncRNA-TBP acts as a regulatory RNA that directly interacts with TBP protein to regulate the transcriptional activity of TBP-target genes (such as KLF4, GPI, TNNI2, and CDKN1A).

Conclusion

Our findings present a novel model about the regulation of LncRNA-TBP, which can regulate the transcriptional activity of TBP-target genes by recruiting TBP protein, thus modulating myogenesis progression and inducing slow-twitch fibers.
Plasma GAS6 predicts mortality risk in acute heart failure patients: insights from the DRAGON-HF trial
Authors: Ma Teng , Huang Rongrong , Xu Yanhua , Lv Yangbo , Liu Yifan , Pan Xin , Dong Jia , Gao Di , Wang Zeyu , Zhang Fenglei , Yan Chunxi , Ong Sang-Bing , Su Yang , Xu Dachun
Published: January 2023

Background

Growth arrest-specific 6 (GAS6) is a vitamin K-dependent protein related to inflammation, fibrosis, as well as platelet function. Genetic ablation of GAS6 in mice protects against cardiac hypertrophy and dysfunction. Nonetheless, the association between plasma GAS6 levels and acute heart failure (AHF) patients is still unknown.

Methods

We measured plasma GAS6 concentrations in 1039 patients with AHF who were enrolled in the DRAGON-HF trial (NCT03727828). Mean follow-up of the study was 889 days. The primary endpoint is all-cause death.

Results

In total, there were 195 primary endpoints of all-cause death and 135 secondary endpoints of cardiovascular death during the mean follow-up duration of 889 days. The higher levels of GAS6 were associated with higher rates of all-cause and cardiovascular death (P < 0.05). Baseline plasma GAS6 levels were still strongly correlated with clinical outcomes in different models after adjustment for clinical factors and N-terminal pro-brain natriuretic peptide (NT-proBNP, P < 0.05). GAS6 could further distinguish the risks of clinical outcomes based on NT-proBNP measurement.

Conclusion

Elevated plasma GAS6 levels were associated with an increased risk of all-cause and cardiovascular death in patients with AHF.

Trial registration NCT03727828 (DRAGON-HF trial) clinicaltrials.gov
Care at the first postnatal hour in two hospitals of the Adequate Birth Project: qualitative analysis of experiences in two stages of the Healthy Birth research
Authors: Gomes Maysa Luduvice , Nicida Lucia Regina de Azevedo , de Oliveira Débora Cecília Chaves , Rodrigues Andreza , Torres Jacqueline Alves , Coutinho Amanda da Trindade Dias , Cravo Beatriz da Silva Soares de Souza , Dantas Juliana Guimarães , Oliveira Thays Basílio , Brandão Patrick , Domingues Rosa Maria Soares Madeira
Published: January 2023

Background

 The Adequate Childbirth Project (PPA) is a quality improvement project that aims to enhance normal delivery and reduce cesarean sections with no clinical indication in the Brazilian supplementary health care system. This study aims to analyze the care model of the first postpartum hour in hospitals that participated in the PPA.

Methods

Qualitative analysis based on the narrative of 102 women attended at two hospitals participating in the evaluative “Healthy Birth” research that analyzed the degree of implementation and the effects of the PPA. We assessed three practices within the first hour after delivery: skin-to-skin contact, breastfeeding and appropriate clamping of the umbilical cord. Data was collected through semi-structured interviews by telephone and submitted to thematic content analysis.

Results

The categories that emerged from the analysis of the results were “Dimension of time and care expressed in the lived experience” and “Interferences in care in the first hour of life”. In the first category, women reported that in the first hour after delivery the newborn was placed on the mother's chest, but the length of time of the newborn's stay in skin-to-skin contact was less than one hour. This experience, even in a shorter period of time, was said to be positive by the women interviewed. Two barriers were observed: interruption of skin-to-skin contact for neonatal care and the transfer to the recovery room, both separating baby from mother without observing the duration of the "golden hour". It was identified that a process of improvement of the quality of care for childbirth is underway, with a gradual incorporation of recommended practices for care in newborn's first hour of life.

Conclusions

Women reported access to the three care practices at two hospitals participating in the PPA quality improvement project. All practices were valued by women as a positive experience and should be promoted. Information during antenatal care to increase women´s autonomy, review of hospital practices to reduce barriers, and support from health care providers during the first hour after birth are needed to improve the implementation of these practices and access to their health benefits.
Feasibility of a combined intermittent theta-burst stimulation and video game-based dexterity training in Parkinson’s disease
Authors: Pastore-Wapp Manuela , Kaufmann Brigitte C. , Nyffeler Thomas , Wapp Simona , Bohlhalter Stephan , Vanbellingen Tim
Published: January 2023

Background

Persons with Parkinson’s disease (PD) often exhibit difficulties with dexterity during the performance of activities of daily living (ADL), inter alia due to dysfunctional supplementary motor area (SMA). Combined intermittent theta-burst stimulation (iTBS) over the SMA followed by video game-based training (VBT) may therefore improve dexterity related ADL. The VBT may induce high flow levels related to high performance during the training. The aim of this study is to evaluate the feasibility of a combined iTBS-VBT intervention in persons with PD.

Methods

A total of nine persons with PD (mean age 63.3 ± 8.76 years) with self-reported difficulties with dexterity related ADL were included in this pilot iTBS-VBT study. All participants received either iTBS or sham stimulation over the SMA followed by a 45-min VBT, three times a week for a total of three weeks. Feasibility was measured by means of the adherence rate and the system usability (System Usability Scale). Moreover, flow was measured after the last VBT session.

Results

Adherence rate was excellent with 100%. High system usability scores (i.e., mean 80%, range 55–97.5) and a significant Spearman’s correlation with the Flow State Scale (r = .762, p = .017) further point to the high feasibility of the VBT. Neither demographic variables nor difficulties in dexterity related ADL affected the usability of the VBT.

Conclusion

This study demonstrates the high feasibility of a combined iTBS-VBT intervention. Moreover, the level of self-reported usability was related to flow experience. Whether this kind of combined iTBS-VBT intervention improves dexterity will be evaluated in a randomized controlled trial.

Trial registration clincaltrials.gov NCT04699149, date of registration 1. June 2021
Effects of non-invasive brain stimulation on motor function after spinal cord injury: a systematic review and meta-analysis
Authors: Chen Jian-Min , Li Xiao-Lu , Pan Qin-He , Yang Ye , Xu Sen-Ming , Xu Jian-Wen
Published: January 2023

Background

In recent years, non-invasive brain stimulation (NIBS) has been used for motor function recovery. However, the effects of NIBS in populations with spinal cord injury (SCI) remain unclear. This study aims to conduct a meta-analysis of the existing evidence on the effects and safety of NIBS against sham groups for motor dysfunction after SCI to provide a reference for clinical decision-making.

Methods

Two investigators systematically screened English articles from PubMed, MEDLINE, Embase, and Cochrane Library for prospective randomized controlled trials regarding the effects of NIBS in motor function recovery after SCI. Studies with at least three sessions of NIBS were included. We assessed the methodological quality of the selected studies using the evidence-based Cochrane Collaboration’s tool. A meta-analysis was performed by pooling the standardized mean difference (SMD) with 95% confidence intervals (CI).

Results

A total of 14 randomized control trials involving 225 participants were included. Nine studies used repetitive transcranial magnetic stimulation (rTMS) and five studies used transcranial direct current stimulation (tDCS). The meta-analysis showed that NIBS could improve the lower extremity strength (SMD = 0.58, 95% CI = 0.02–1.14, P = 0.004), balance (SMD = 0.64, 95% CI = 0.05–1.24, P = 0.03), and decrease the spasticity (SMD = − 0.64, 95% CI = − 1.20 to − 0.03, P = 0.04). However, the motor ability of the upper extremity in the NIBS groups was not statistically significant compared with those in the control groups (upper-extremity strength: P = 0.97; function: P = 0.56; and spasticity: P = 0.12). The functional mobility in the NIBS groups did not reach statistical significance when compared with the sham NIBS groups (sham groups). Only one patient reported seizures that occurred during stimulation, and no other types of serious adverse events were reported.

Conclusion

NIBS appears to positively affect the motor function of the lower extremities in SCI patients, despite the marginal P-value and the high heterogeneity. Further high-quality clinical trials are needed to support or refute the use and optimize the stimulation parameters of NIBS in clinical practice.
Individual brain regulation as learned via neurofeedback is related to affective changes in adolescents with autism spectrum disorder
Authors: Klöbl Manfred , Prillinger Karin , Diehm Robert , Doganay Kamer , Lanzenberger Rupert , Poustka Luise , Plener Paul , Konicar Lilian
Published: January 2023

Background

Emotions often play a role in neurofeedback (NF) regulation strategies. However, investigations of the relationship between the induced neuronal changes and improvements in affective domains are scarce in electroencephalography-based studies. Thus, we extended the findings of the first study on slow cortical potential (SCP) NF in autism spectrum disorder (ASD) by linking affective changes to whole-brain activity during rest and regulation.

Methods

Forty-one male adolescents with ASD were scanned twice at rest using functional magnetic resonance imaging. Between scans, half underwent NF training, whereas the other half received treatment as usual. Furthermore, parents reported on their child’s affective characteristics at each measurement. The NF group had to alternatingly produce negative and positive SCP shifts during training and was additionally scanned using functional magnetic resonance imaging while applying their developed regulation strategies.

Results

No significant treatment group-by-time interactions in affective or resting-state measures were found. However, we found increases of resting activity in the anterior cingulate cortex and right inferior temporal gyrus as well as improvements in affective characteristics over both groups. Activation corresponding to SCP differentiation in these regions correlated with the affective improvements. A further correlation was found for Rolandic operculum activation corresponding to positive SCP shifts. There were no significant correlations with the respective achieved SCP regulation during NF training.

Conclusion

SCP NF in ASD did not lead to superior improvements in neuronal or affective functioning compared to treatment as usual. However, the affective changes might be related to the individual strategies and their corresponding activation patterns as indicated by significant correlations on the whole-brain level.

Trial registration This clinical trial was registered at drks.de (DRKS00012339) on 20th April, 2017.
Circadian rhythms in the blood–brain barrier: impact on neurological disorders and stress responses
Authors: Schurhoff Nicolette , Toborek Michal
Published: January 2023

Circadian disruption has become more prevalent in society due to the increase in shift work, sleep disruption, blue light exposure, and travel via different time zones. The circadian rhythm is a timed transcription-translation feedback loop with positive regulators, BMAL1 and CLOCK, that interact with negative regulators, CRY and PER, to regulate both the central and peripheral clocks. This review highlights the functions of the circadian rhythm, specifically in the blood–brain barrier (BBB), during both healthy and pathological states. The BBB is a highly selective dynamic interface composed of CNS endothelial cells, astrocytes, pericytes, neurons, and microglia that form the neurovascular unit (NVU). Circadian rhythms modulate BBB integrity through regulating oscillations of tight junction proteins, assisting in functions of the NVU, and modulating transporter functions. Circadian disruptions within the BBB have been observed in stress responses and several neurological disorders, including brain metastasis, epilepsy, Alzheimer’s disease, and Parkinson’s disease. Further understanding of these interactions may facilitate the development of improved treatment options and preventative measures.
Temporal trends in mortality and provision of intensive care in younger women and men with acute myocardial infarction or stroke
Authors: Arslani Ketina , Tontsch Janna , Todorov Atanas , Gysi Bianca , Kaufmann Mark , Kaufmann Fabian , Hollinger Alexa , Wildi Karin , Merdji Hamid , Helms Julie , Siegemund Martin , Gebhard Catherine , Gebhard Caroline E. ,   on behalf of the Swiss Society of Intensive Care Medicine
Published: January 2023

Background

Timely management of acute myocardial infarction (AMI) and acute stroke has undergone impressive progress during the last decade. However, it is currently unknown whether both sexes have profited equally from improved strategies. We sought to analyze sex-specific temporal trends in intensive care unit (ICU) admission and mortality in younger patients presenting with AMI or stroke in Switzerland.

Methods

Retrospective analysis of temporal trends in 16,954 younger patients aged 18 to ≤ 52 years with AMI or acute stroke admitted to Swiss ICUs between 01/2008 and 12/2019.

Results

Over a period of 12 years, ICU admissions for AMI decreased more in women than in men (− 6.4% in women versus − 4.5% in men, p < 0.001), while ICU mortality for AMI significantly increased in women (OR 1.2 [1.10–1.30], p = 0.032), but remained unchanged in men (OR 0.99 [0.94–1.03], p = 0.71). In stroke patients, ICU admission rates increased between 3.6 and 4.1% per year in both sexes, while ICU mortality tended to decrease only in women (OR 0.91 [0.85–0.95, p = 0.057], but remained essentially unaltered in men (OR 0.99 [0.94–1.03], p = 0.75). Interventions aimed at restoring tissue perfusion were more often performed in men with AMI, while no sex difference was noted in neurovascular interventions.

Conclusion

Sex and gender disparities in disease management and outcomes persist in the era of modern interventional neurology and cardiology with opposite trends observed in younger stroke and AMI patients admitted to intensive care. Although our study has several limitations, our data suggest that management and selection criteria for ICU admission, particularly in younger women with AMI, should be carefully reassessed.

Graphical Abstract
Artifact-free fat-water separation in Dixon MRI using deep learning
Authors: Basty Nicolas , Thanaj Marjola , Cule Madeleine , Sorokin Elena P. , Liu Yi , Thomas E. Louise , Bell Jimmy D. , Whitcher Brandon
Published: January 2023

Chemical-shift encoded MRI (CSE-MRI) is a widely used technique for the study of body composition and metabolic disorders, where derived fat and water signals enable the quantification of adipose tissue and muscle. The UK Biobank is acquiring whole-body Dixon MRI (a specific implementation of CSE-MRI) for over 100,000 participants. Current processing methods associated with large whole-body volumes are time intensive and prone to artifacts during fat-water separation performed by the scanner, making quantitative analysis challenging. The most common artifacts are fat-water swaps, where the labels are inverted at the voxel level. It is common for researchers to discard swapped data (generally around 10%), which is wasteful and may lead to unintended biases. Given the large number of whole-body Dixon MRI acquisitions in the UK Biobank, thousands of swaps are expected to be present in the fat and water volumes from image reconstruction performed on the scanner. If they go undetected, errors will propagate into processes such as organ segmentation, and dilute the results in population-based analyses. There is a clear need for a robust method to accurately separate fat and water volumes in big data collections like the UK Biobank. We formulate fat-water separation as a style transfer problem, where swap-free fat and water volumes are predicted from the acquired Dixon MRI data using a conditional generative adversarial network, and introduce a new loss function for the generator model. Our method is able to predict highly accurate fat and water volumes free from artifacts in the UK Biobank. We show that our model separates fat and water volumes using either single input (in-phase only) or dual input (in-phase and opposed-phase) data, with the latter producing superior results. Our proposed method enables faster and more accurate downstream analysis of body composition from Dixon MRI in population studies by eliminating the need for visual inspection or discarding data due to fat-water swaps.
Effect of Oral Contraception on Screening Tests for Primary Aldosteronism: A 10-Year Longitudinal Study
Authors: Yang Jun , Gwini Stella May , Beilin Lawrence J , Schlaich Markus , Stowasser Michael , Young Morag J , Fuller Peter J , Mori Trevor A
Published: January 2023

Context

Primary aldosteronism (PA) and oral contraception (OC) can both cause hypertension in young women. However, the effect of OC on the screening test for PA, the aldosterone to renin ratio (ARR), is not clear.

Objective

We evaluated the impact of OC on the screening test for PA.

Methods

In this retrospective cohort study, we analyzed data from the female offspring (Gen2) of women enrolled in the Raine Study, a population-based birth cohort, who had blood pressure (BP) measurements, blood samples, and information about OC use at age 17 years (N = 484) and/or age 27 years (N = 486).

Results

Aldosterone concentration was significantly higher in OC users than nonusers at 17 years (median 486 pmol/L vs 347 pmol/L, P < 0.001). Renin concentration was significantly lower in OC users at both 17 years (13.4 mU/L vs 20.6 mU/L) and 27 years (9.2 mU/L vs 11.8 mU/L), hence the ARR was significantly higher in OC users compared to nonusers at both 17 years (31.5 vs 18.3) and 27 years (27.3 vs 21.1). The proportion of participants with ARR > 70 pmol/mU (current threshold for PA detection) was significantly higher in OC users at both 17 years (12.6% vs 2.1%) and 27 years (6.4% vs 0.4%); however, they had comparable BP to those with ARR < 70. OC use at any age abolished the relationship between ARR and BP that is observed in nonusers.

Conclusion

OC can increase the ARR and cause a false positive PA screening result. Until more reliable criteria for PA screening in OC users are established, alternative contraception should be considered during screening.
Sex Hormones and Diabetes in 45- to 74-year-old Men and Postmenopausal Women: The Hispanic Community Health Study
Authors: Persky Victoria , Abasilim Chibuzor , Tsintsifas Konstantina , Day Tessa , Sargis Robert M , Daviglus Martha L , Cai Jianwen , Freels Sally , Unterman Terry , Chavez Noel , Kaplan Robert , Isasi Carmen R , Pirzada Amber , Meyer Michelle L , Talavera Gregory A , Thyagarajan Bharat , Peters Brandilyn A , Madrigal Jessica M , Grieco Arielle , Turyk Mary E
Published: January 2023

Previous studies demonstrated associations of endogenous sex hormones with diabetes. Less is known about their dynamic relationship with diabetes progression through different stages of the disease, independence of associations, and role of the hypothalamic-pituitary gonadal axis.

The purpose of this analysis was to examine relationships of endogenous sex hormones with incident diabetes, prediabetes, and diabetes traits in 693 postmenopausal women and 1015 men aged 45 to 74 years without diabetes at baseline participating in the Hispanic Community Health Study/Study of Latinos and followed for 6 years. Baseline hormones included estradiol, luteinizing hormone (LH), follicle stimulating hormone (FSH), sex hormone-binding globulin (SHBG), dehydroepiandrosterone sulfate (DHEAS), and, in men, testosterone and bioavailable testosterone. Associations were analyzed using multivariable Poisson and linear regressions. In men, testosterone was inversely associated with conversion from prediabetes to diabetes (incidence rate ratio [IRR] for 1 SD increase in testosterone: 0.821; 95% CI, 0.676, 0.997; P = 0.046), but not conversion from normoglycemia to prediabetes. Estradiol was positively associated with increase in fasting insulin and homeostatic model assessment of insulin resistance. In women, SHBG was inversely associated with change in glycosylated hemoglobin, postload glucose, and conversion from prediabetes to diabetes (IRR = 0.62; 95% CI, 0.44, 0.86, P = 0.005) but not from normoglycemia to prediabetes. Relationships with other hormones varied across glycemic measures. Stronger associations of testosterone and SHBG with transition from prediabetes to diabetes than from normoglycemic to prediabetes suggest they are operative at later stages of diabetes development. Biologic pathways by which sex hormones affect glucose homeostasis await future studies.
Going with the flow – how a stream insect, Pteronarcys californica, exploits local flows to increase oxygen availability
Authors: Birrell Jackson H. , Woods H. Arthur
Published: January 2023

For insects, life in water is challenging because oxygen supply is typically low compared with in air. Oxygen limitation may occur when oxygen levels or water flows are low or when warm temperatures stimulate metabolic demand for oxygen. A potential mechanism for mitigating oxygen shortages is behavior – moving to cooler, more oxygenated or faster flowing microhabitats. Whether stream insects can make meaningful choices, however, depends on: (i) how temperature, oxygen and flow vary at microspatial scales and (ii) the ability of insects to sense and exploit that variation. To assess the extent of microspatial variation in conditions, we measured temperature, oxygen saturation and flow velocity within riffles of two streams in Montana, USA. In the lab, we then examined preferences of nymphs of the stonefly Pteronarcys californica to experimental gradients based on field-measured values. Temperature and oxygen level varied only slightly within stream riffles. By contrast, flow velocity was highly heterogeneous, often varying by more than 125 cm s−1 within riffles and 44 cm s−1 around individual cobbles. Exploiting micro-variation in flow may thus be the most reliable option for altering rates of oxygen transport. In support of this prediction, P. californica showed little ability to exploit gradients in temperature and oxygen but readily exploited micro-variation in flow – consistently choosing higher flows when conditions were warm or hypoxic. These behaviors may help stream insects mitigate low-oxygen stress from climate change and other anthropogenic disturbances.
One size does not fit all: diversity of length–force properties of obliquely striated muscles
Authors: Thompson Joseph T. , Taylor-Burt Kari R. , Kier William M.
Published: January 2023

Obliquely striated muscles occur in 17+ phyla, likely evolving repeatedly, yet the implications of oblique striation for muscle function are unknown. Contrary to the belief that oblique striation allows high force output over extraordinary length ranges (i.e. superelongation), recent work suggests diversity in operating length ranges and length–force relationships. We hypothesize oblique striation evolved to increase length–force relationship flexibility. We predict that superelongation is not a general characteristic of obliquely striated muscles and instead that length–force relationships vary with operating length range. To test these predictions, we measured length–force relationships of five obliquely striated muscles from inshore longfin squid, Doryteuthis pealeii: tentacle, funnel retractor and head retractor longitudinal fibers, and arm and fin transverse fibers. Consistent with superelongation, the tentacle length–force relationship had a long descending limb, whereas all others exhibited limited descending limbs. The ascending limb at 0.6P0 was significantly broader (P<0.001) for the tentacle length–force relationship (0.43±0.04L0; where L0 is the preparation length that produced peak isometric stress, P0) than for the arm (0.29±0.03L0), head retractor (0.24±0.06L0), fin (0.20±0.04L0) and funnel retractor (0.27±0.03L0). The fin's narrow ascending limb differed significantly from those of the arm (P=0.004) and funnel retractor (P=0.012). We further characterized the tentacle preparation's maximum isometric stress (315±78 kPa), maximum unloaded shortening velocity (2.97±0.55L0 s−1) and ultrastructural traits (compared with the arm), which may explain its broader length–force relationship. Comparison of obliquely striated muscles across taxa revealed length–force relationship diversity, with only two species exhibiting superelongation.
Anchor threads can double the insect flight energy absorbed by spider orb webs
Authors: Han Sarah I. , Alicea-Serrano Angela M. , Blackledge Todd A.
Published: January 2023

To successfully capture flying insect prey, a spider's orb web must withstand the energy of impact without the silk breaking. In this study, we examined the anchor threads: the silk lines that anchor the main capture area of the web to the surrounding environment. These anchor threads can account for a large portion of the web, yet are usually excluded from experiments and simulations. We compared projectile capture and kinetic energy absorption between webs with and without access to anchor threads. Webs with anchor threads captured significantly more projectiles and absorbed significantly more energy than those with constrained anchors. This is likely because the anchor threads increase web compliance, resulting in webs with the ability to catch high-energy flying insects without breaking. Anchor threads are one example of how different types of web architecture expand the range of possible prey capture strategies by enabling the web to withstand greater impacts.