bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transcutaneous Electrical Cranial-Auricular Acupoint Stimulation vs. Escitalopram for Patients With Mild-to-Moderate Depression (TECAS): Study Design for a Randomized Controlled, Non-inferiority Trial
Authors: Yang Sichang , Qin Zongshi , Yang Xinjing , Chan Mei Yan , Zhang Shuiyan , Rong Peijing , Hou Xiaobing , Jin Guixing , Xu Fengquan , Liu Yong , Zhang Zhang-Jin 
Published: May 2022

BackgroundPrevious studies in animals and humans indicated that transcutaneous vagus nerve stimulation (tVNS) and transcutaneous electrical acupoint stimulation (TEAS) on trigeminal nerve-innervated forehead acupoints can relief the symptoms of depression. However, due to the limited investigations on these two interventions, more research are needed to confirm their efficacy in depression. To improve the efficacy of the single treatment, we combined two treatments and created a novel non-invasive stimulation, transcutaneous electrical cranial-auricular acupoint stimulation (TECAS). To assess the efficacy and safety of TECAS, we compare it with a selective serotonin reuptake inhibitor (SSRI), escitalopram, for the treatment of depression.Methods/DesignThis is a multi-center, non-inferiority, randomized controlled trial that will involve 470 patients with mild to moderate depression. Patients will be randomly assigned to either the TECAS group or the escitalopram group in a 1:1 ratio. The TEAS group will receive two sessions of treatments per day for 8 consecutive weeks, and the escitalopram group will receive 8 weeks of oral escitalopram tablets prescribed by clinical psychiatrists as appropriate for their condition. The primary outcome is the clinical response as determined by Montgomery-Åsberg Depression Rating Scale (MADRS) scores at week 8, with −10% as the non-inferior margin. The secondary outcomes include the response rate determined by 17-item Hamilton Depression Rating Scale (HAMD-17), remission rate, changes from baseline in the scores on the MADRS, the HAMD-17, the Hamilton Anxiety Rating Scale (HAMA), the Pittsburgh Sleep Quality Index (PSQI), and the Short Form 36 Health Survey (SF-36).DiscussionThis will be the first randomized controlled trial to compare the efficacy of TECAS with escitalopram for depression. If effective, this novel intervention could have significant clinical and research implications for patients with depression.Clinical Trial Registration[ClinicalTrials.gov], identifier [NCT03909217].
Alterations of Resting-State Locus Coeruleus Functional Connectivity After Transdermal Trigeminal Electrical Neuromodulation in Insomnia
Authors: Um Yoo Hyun , Wang Sheng-Min , Kang Dong Woo , Kim Nak-Young , Lim Hyun Kook 
Published: May 2022

BackgroundTransdermal trigeminal electrical neuromodulation (TTEN) is a novel treatment modality that is known for noradrenergic modulation through the trigeminal nerve and locus coeruleus (LC). This study aimed to demonstrate the alterations of LC functional connectivity (FC) in patients with insomnia after a 4-week TTEN.MethodsThe Cefaly device targeting the ophthalmic division of the trigeminal nerve was applied to a total of 12 patients with insomnia to monitor for the effects of TTEN. All the patients went through a 4-week daily 20 min TTEN sessions before bedtime. Baseline and post-TTEN demographic data, polysomnography (PSG) parameters, and insomnia severity index (ISI) were attained. Data from pre- and post-intervention resting-state functional magnetic resonance imaging (MRI) were collected. LC FC differences were measured between the pre-and post-TTEN groups through seed-to-voxel analysis. Correlation analyses were conducted between LC FC changes after TTEN, ISI score changes, and PSG parameter changes.ResultsThere was a significantly decreased LC FC with occipital and temporal cortices after a 4-week TTEN. However, there was no significant correlation between LC FC, ISI score changes, and PSG parameter changes.ConclusionBy targeting hyperarousal symptoms of insomnia, TTEN can be a promising intervention that can modulate LC FC in patients with insomnia patients. The data presented in the study are from a study exploring the effect of TTEN on insomnia (www.clinicaltrials.gov, NCT04838067).
From Perceived Stress to Demoralization in Parkinson Disease: A Path Analysis
Authors: de Figueiredo John M. , Zhu Boheng , Patel Amar , Kohn Robert , Koo Brian B. , Louis Elan D. 
Published: May 2022

ObjectivesThe objective of this study was to determine whether depression and anxiety are mediators between perceived stress and demoralization via a loss of the cognitive map to get out of the predicament manifesting as subjective incompetence.MethodsNinety-five consecutive outpatients with Parkinson's disease were evaluated for perceived stress, depression, anxiety, subjective incompetence, and demoralization using reliable and valid scales. Inclusion criteria were ages 40–90, intact cognition, and no current history of substance use. The setting was a Movement Disorders Clinic at a university-affiliated hospital. The outcome variable was demoralization, selecteda priori. Mediators between perceived stress and demoralization were examined using path analysis.ResultsDepression, anxiety, and subjective incompetence were mediators between perceived stress and demoralization. Among all variables, subjective incompetence was the largest contributor to demoralization. Depression connected to demoralization indirectly via subjective incompetence (β = 0.25,p&lt; 0.001), whereas anxiety bypassed subjective incompetence (β = −0.01,p= 0.882), connecting directly to demoralization (β = 0.37,p= 0.008).ConclusionEarly treatment and reversal of subjective incompetence and anxiety could potentially prevent the escalation of demoralization and the associated disruption in health-related quality of life and eventual suicide.
Altered White Matter Integrity at Illness Onset in Adolescents With a First Episode of Psychosis
Authors: Romero Soledad , de la Serna Elena , Baeza Inmaculada , Valli Isabel , Pariente José Carlos , Picado Marisol , Bargalló Nuria , Sugranyes Gisela , Castro-Fornieles Josefina 
Published: May 2022

BackgroundDisruption in white matter integrity has been consistently observed in individuals with psychosis. However, whether such abnormalities are already present at illness onset or are related to downstream processes remains elusive. The study of adolescents with a recent onset of psychosis provides the opportunity to evaluate white matter integrity proximally to disease onset.MethodsTwenty-six adolescents (aged 15.9 ± 1.3 years) with a first episode of psychosis (FEP) (less than 6 months duration) were compared with 26 age and sex-matched healthy controls (HC) (16.8 ± 2 years). In participants with a FEP, clinical diagnoses were confirmed after a minimum of 1 year follow-up (main categories: schizophrenia, bipolar disorder, or schizoaffective disorder). Anatomical images and diffusion tensor sequences were acquired using a 1.5T scanner. Whole brain, voxel-wise group differences in fractional anisotropy (FA) were investigated between participants with a FEP and controls.ResultsRelative to HC, FEP participants displayed decreased FA in the right posterior cingulate gyrus, encompassing the right superior and posterior corona radiata, and the right parahippocampal gyrus, including the cingulum and fornix. FEP patients showed no areas of increased FA relative to HC. The results remained significant after controlling for medication, cannabis use and intelligence.ConclusionOur findings indicate that adolescents with recent onset of psychotic disorders show decreased white matter integrity in circuits implicated in cognitive functions and emotion regulation.
Integrated Management of Diabetes and Tuberculosis in Rural India – Results From a Pilot Study
Authors: Joshi Rohina , Behera Deepanjali , Di Tanna Gian Luca , Ameer Mohammed Abdul , Yakubu Kenneth , Praveen Devarsetty 
Published: May 2022

IntroductionThe World Health Organization and International Union against Tuberculosis (TB) recommends screening patients with TB for Diabetes Mellitus (DM) at the initiation of treatment. There are few pilot studies which screen TB patients for DM, but none of them have documented the feasibility of managing TB patients with DM in the Indian healthcare setting. Operational research is needed to determine the best way to manage individuals with both conditions. This pilot study aimed to develop, and field test an integrated, multidisciplinary program addressing the management of individuals with TB and DM and other associated chronic conditions in the Indian primary healthcare setting.MethodsThis pilot study used a randomized controlled trial design with mixed-methods evaluation and was conducted in Guntur district of Andhra Pradesh, a southern state of India. All the 120 patients newly diagnosed with TB from 10 participating villages were screened for DM and associated cardiovascular risk factors. Non-physician health workers were trained to follow-up patients for a period of 8 months to encourage treatment adherence, monitor treatment response including blood glucose levels and provide lifestyle advice.ResultsThe intervention was well-accepted by the providers and patients. However, there were no statistically significant variations observed for mean blood glucose levels (mean [SD]: 5.3 [−23.3 to 33.8]) of patients for both intervention and control group participants in this feasibility study. Awareness about diabetes and tuberculosis comorbidity and cardiovascular risk increased among the non-physician health workers in the intervention arm of the study.DiscussionThe co-management of TB-DM is acceptable to both the health providers and patients. With appropriate training, availability of infrastructure and planned intervention implementation, it is feasible to co-manage TB-DM within the existing primary health care system in India.
Lenvatinib Plus Pembrolizumab vs. Chemotherapy in Pretreated Patients With Advanced Endometrial Cancer: A Cost-Effectiveness Analysis
Authors: Feng Mingyang , Chen Yue , Yang Yang , Li Qiu 
Published: May 2022

BackgroundIn the international, randomized, open-label, phase 3 study 309-KEYNOTE-775 trial, lenvatinib plus pembrolizumab (LP) showed improved progression-free survival (PFS) and overall survival (OS) compared with chemotherapy in pretreated patients with advanced endometrial cancer. This study aimed to investigate whether LP is cost-effective compared with chemotherapy.Materials and MethodsThe clinical data for this model was derived from the 309-KEYNOTE-775 trial. Costs and utilities were either derived from the standard fee database or extracted from previously published literature. A three-state Markov model was developed to simulate the disease process of patients with advanced endometrial cancer. One-way sensitivity analyses were conducted to investigate the impact of variables in the analysis model. Probabilistic sensitivity analysis was performed based on 10,000 Monte-Carlo simulations. A subgroup analysis was performed to test whether LP is cost-effective in patients with mismatch repair–proficient (pMMR) disease.ResultsLenvatinib plus pembrolizumab provided an incremental 0.64 quality-adjusted life years (QALYs) with an incremental cost of $241,278.18, compared with chemotherapy, resulting in the incremental cost-effectiveness ratio (ICER) of $378,251.44/QALY, which exceeded the willingness to pay (WTP) threshold. While in the pMMR subgroup, the ICER increased to $413,256.68/QALY. The variance of the utility of PFS state, the cost of LP, and the utility of the progressive disease state were the most influential factors in the sensitivity analysis.ConclusionUnder the current WTP threshold, LP is not cost-effective compared with chemotherapy in pretreated patients with advanced endometrial cancer.
Application of Intraoperative Ultrasound Navigation in Neurosurgery
Authors: Simfukwe Keith , Iakimov Iurii , Sufianov Rinat , Borba Luís , Mastronardi Luciano , Shumadalova Alina 
Published: May 2022

Effective intraoperative image navigation techniques are necessary in modern neurosurgery. In the last decade, intraoperative ultrasonography (iUS), a relatively inexpensive procedure, has gained widespread acceptance.AimTo document and describe the neurosurgery cases, in which iUS has been employed as the primary navigational tool. This includes a discussion of the advantages that iUS may possess relative to other forms of neuronavigation.ConclusionThe application of iUS as an intraoperative navigation tool during neurosurgery holds great potential as it has been shown, relative to other neuronavigation techniques, to be quick, repeatable, and able to provide real-time results.
Identification of Key Genes Associated With Early Calf-Hood Nutrition in Subcutaneous and Visceral Adipose Tissues by Co-Expression Analysis
Authors: Pan Cuili , Yang Chaoyun , Ma Yanfen , Sheng Hui , Lei Zhaoxiong , Wang Shuzhe , Hu Honghong , Feng Xue , Zhang Junxing , Ma Yun 
Published: May 2022

BackgroundSubstantive evidence has confirmed that nutrition state is associated with health risk and the onset of pubertal and metabolic profile. Due to heterogeneity, adipose tissues in different anatomical positions tend to show various metabolic mechanisms for nutrition. To date, the complicated molecular mechanisms of early calf-hood nutrition on bovine adipose tissue are still largely unknown. This study aimed to identify key genes and functionally enriched pathways associated with early calf-hood nutrition in visceral and subcutaneous adipose tissue.ResultsThe RNA-seq data of visceral and subcutaneous adipose tissues of calves feeding on low and high dietary nutrition for more than 100 days were downloaded and analyzed by weighted gene co-expression network analysis (WGCNA). Two modules that positively associated with a low plane of nutrition diet and two modules with a high plane of nutrition diet were identified in the subcutaneous adipose tissue. The blue and yellow modules, most closely associated with low and high nutrition, were selected for the functional enrichment analysis and exploration of hub genes. The results showed that genes in the blue module were significantly enriched in pathways that related to fat metabolism, reproduction, and cell communication. Genes in the yellow module were enriched in pathways related to fat metabolism, reproduction, cell proliferation, and senescence. Meanwhile, the blue and brown modules in visceral adipose tissue were most closely associated with low and high nutrition, respectively. Notably, genes of the blue module were significantly enriched in pathways related to substance metabolism, and genes in the brown module were significantly enriched in energy metabolism and disease pathways. Finally, key genes in subcutaneous adipose tissue for low nutrition (PLCG1, GNA11, and ANXA5) and high nutrition (BUB1B, ASPM, RRM2, PBK, NCAPG, and MKI67), and visceral adipose tissue for low nutrition (RPS5, RPL4, RPL14, and RPLP0) and high nutrition (SDHA and AKT1) were obtained and verified.ConclusionThe study applied WGCNA to identify hub genes and functionally enriched pathways in subcutaneous and visceral adipose tissue and provided a basis for studying the effect of early calf-hood nutrition on the two adipose tissue types.
SARS-CoV-2 Infection Can Lead to an Increase in Tacrolimus Levels in Renal Transplant Patients: A Cohort Study
Authors: Chalklin Christopher G. , Koimtzis Georgios , Khalid Usman , Carrington-Windo Eliot , Elker Doruk , Asderakis Argiris 
Published: May 2022

The aim of this study is to evaluate the effect of SARS-CoV-2 infection on serum tacrolimus levels. Tacrolimus levels of 34 transplant patients diagnosed with SARS-CoV-2 in 2020 were compared with their pre-infection values and those of a control group with alternative infections. 20 out of 34 (59%) had high levels. At diagnosis, median tacrolimus level in the SARS-CoV-2 cohort was 9.6 μg/L (2.7–23) compared to 7.9 μg/L in the control group (p = 0.07, 95% CI for difference −0.3–5.8). The ratio of post-infection to pre-infection tacrolimus values was higher in the SARS-CoV-2 group (1.7) compared to the control group (1.25, p = 0.018, 95% CI for difference 0.08–0.89). The acute kidney injury rate was 65% (13 of 20) in SARS-CoV-2 patients with a level &gt;8 μg/dl, compared to 29% (4 of 14) in those with lower levels (p = 0.037). Median length of stay was 10 days among SARS-CoV-2 infected patients with high tacrolimus levels compared to 0 days in the rest (p = 0.04). Four patients with high levels died compared to 2 in the control group. Clinicians should be aware of this potential effect on tacrolimus levels and take appropriate measures.
Post-Transplant Extracorporeal Membrane Oxygenation for Severe Primary Graft Dysfunction to Support the Use of Marginal Donor Hearts
Authors: Shudo Yasuhiro , Alassar Aiman , Wang Hanjay , Lingala Bharathi , He Hao , Zhu Yuanjia , Hiesinger William , MacArthur John W. , Boyd Jack H. , Lee Anson M. , Currie Maria , Woo Y. Joseph 
Published: May 2022

Severe primary graft dysfunction (PGD) is the leading cause of early postoperative mortality following orthotopic heart transplantation (OHT). Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) has been used as salvage therapy. This study aimed to evaluate the outcomes in adult OHT recipients who underwent VA-ECMO for severe PGD. We retrospectively reviewed 899 adult (≥18 years) patients who underwent primary OHT at our institution between 1997 and 2017. Recipients treated with VA-ECMO (19, 2.1%) exhibited a higher incidence of previous cardiac surgery (p = .0220), chronic obstructive pulmonary disease (p = .0352), and treatment with a calcium channel blocker (p = .0018) and amiodarone (p = .0148). Cardiopulmonary bypass (p = .0410) and aortic cross-clamp times (p = .0477) were longer in the VA-ECMO cohort and they were more likely to have received postoperative transfusion (p = .0013); intra-aortic balloon pump (IABP, p &lt; .0001), and reoperation for bleeding or tamponade (p &lt; .0001). The 30-day, 1-year, and overall survival after transplantation of non-ECMO patients were 95.9, 88.8, and 67.4%, respectively, compared to 73.7, 57.9, and 47.4%, respectively in the ECMO cohort. Fourteen (73.7%) of the ECMO patients were weaned after a median of 7 days following OHT (range: 1–12 days). Following OHT, VA-ECMO may be a useful salvage therapy for severe PGD and can potentially support the usage of marginal donor hearts.
Epidemiological Study of Tricuspid Regurgitation After Cardiac Transplantation. Does it Influence Survival?
Authors: López-Vilella Raquel , Paniagua-Martín María J. , González-Vílchez Francisco , Donoso Trenado Víctor , Barge-Caballero Eduardo , Sánchez-Lázaro Ignacio , Aller Fernández Ana V. , Martínez-Dolz Luis , Crespo-Leiro María G. , Almenar-Bonet Luis 
Published: May 2022

Background: Tricuspid valve disease is the most frequent valvulopathy after heart transplantation (HTx). Evidence for the negative effect of post-transplant tricuspid regurgitation (TR) on survival is contradictory. The aim of this study was to analyze the causes of post-transplant TR and its effect on overall mortality.Methods: This is a retrospective observational study of all transplants performed in two Spanish centers (1009 patients) between 2000 and 2019. Of the total number of patients, 809 had no TR or mild TR and 200 had moderate or severe TR. The etiology of TR was analyzed in all cases.Results: The prevalence of moderate and severe TR was 19.8%. The risk of mortality was greater when TR was caused by early primary graft failure (PGF) or rejection (p &lt; 0.05). TR incidence was related to etiology: incidence of PGF-induced TR was higher in the first period, while TR due to rejection and undefined causes occurred more frequently in three periods: in the first year, in the 10–14-year period following HTx, and in the long term (16–18 years). In the multivariable analysis, TR was significantly associated with mortality/retransplantation (HR:1.04, 95% CI:1.01–1.07, p:0.02).Conclusion: The development of TR after HTx is relatively frequent. The annual incidence depends on TR severity and etiology. The risk of mortality is greater in severe TR due to PGF or rejection.
Immune Response to Third Dose BNT162b2 COVID-19 Vaccine Among Kidney Transplant Recipients—A Prospective Study
Authors: Yahav Dafna , Rahamimov Ruth , Mashraki Tiki , Ben-Dor Naomi , Steinmetz Tali , Agur Timna , Zingerman Boris , Herman-Edelstein Michal , Lichtenberg Shelly , Ben-Zvi Haim , Bar-Haim Erez , Cohen Hila , Rotem Shahar , Elia Uri , Margalit Ili , Zvi Benaya Rozen 
Published: May 2022

Immune response to two SARS-CoV-2 mRNA vaccine doses among kidney transplant recipients (KTRs) is limited. We aimed to evaluate humoral and cellular response to a third BNT162b2 dose. In this prospective study, 190 KTRs were evaluated before and ∼3 weeks after the third vaccine dose. The primary outcomes were anti-spike antibody level &gt;4160 AU/ml (neutralization-associated cutoff) and any seropositivity. Univariate and multivariate analyses were conducted to identify variables associated with antibody response. T-cell response was evaluated in a subset of participants. Results were compared to a control group of 56 healthcare workers. Among KTRs, we found a seropositivity rate of 70% (133/190) after the third dose (37%, 70/190, after the second vaccine dose); and 27% (52/190) achieved levels above 4160 AU/ml after the third dose, compared to 93% of controls. Variables associated with antibody response included higher antibody levels after the second dose (odds ratio [OR] 30.8 per log AU/ml, 95% confidence interval [CI]11–86.4, p &lt; 0.001); and discontinuation of antimetabolite prior to vaccination (OR 9.1,95% CI 1.8–46.5, p = 0.008). T-cell response was demonstrated in 13% (7/53). In conclusion, third dose BNT162b2 improved immune response among KTRs, however 30% still remained seronegative. Pre-vaccination temporary immunosuppression reduction improved antibody response.
Impact of Size Matching Based on Donor-Recipient Height on Kidney Transplant Outcomes
Authors: Tandukar Srijan , Wu Christine , Hariharan Sundaram , Puttarajappa Chethan 
Published: May 2022

Transplantation of kidneys from shorter donors into taller recipients may lead to suboptimal allograft survival. The effect of discrepancy in donor and recipient heights (ΔHeight) on long term transplant outcomes is not known. Adult patients ≥18 years undergoing living or deceased donor (LD or DD) kidney transplants alone from donors ≥18 years between 2000 and 2016 in the United States were included in this observational study. The cohort was divided into three groups based on ΔHeight of 5 inches as 1) Recipient &lt; Donor (DD: 31,688, LD: 12,384), 2) Recipient = Donor (DD: 84,711, LD: 54,709), and 3) Recipient &gt; Donor (DD: 21,741, LD: 18,753). Univariate analysis showed a higher risk of DCGL and mortality in both DD and LD (p &lt; 0.001 for both). The absolute difference in graft and patient survival between the two extremes of ΔHeight was 5.7% and 5.7% for DD, and 0.4% and 1.4% for LD. On multivariate analysis, the HR of DCGL for Recipient &lt; Donor and Recipient &gt; Donor was 0.95 (p = 0.05) and 1.07 (p = 0.01) in DD and 0.98 (p = 0.55) and 1.14 (p &lt; 0.001) in LD. Similarly, the corresponding HR of mortality were 0.97 (p = 0.07) and 1.07 (p = 0.003) for DD and 1.01 (p &lt; 0.001) and 1.05 (p = 0.13) for LD. For DGF, the HR were 1.04 (p = 0.1) and 1.01 (p = 0.7) for DD and 1.07 (p = 0.45) and 0.89 (p = 0.13) for LD. Height mismatch between the donor and recipient influences kidney transplant outcomes.