bluuebunny/crossref_metadata_2025 huggingface dataset:
Transcription factors ZmNF-YA1 and ZmNF-YB16 regulate plant growth and drought tolerance in maize
Authors: Yang Yaling , Wang Baomei , Wang Jiemin , He Chunmei , Zhang Dengfeng , Li Peng , Zhang Juren , Li Zhaoxia
Published: July 2022

The identification of drought stress regulatory genes is crucial for the genetic improvement of maize (Zea mays L.) yield. Nuclear factors Y (NF-Ys) are important transcription factors, but their roles in the drought stress tolerance of plants and underlying molecular mechanisms are largely unknown. In this work, we used yeast two-hybrid screening to identify potential interactors of ZmNF-YB16 and confirmed the interaction between ZmNF-YA1 and ZmNF-YB16-YC17 and between ZmNF-YA7 and ZmNF-YB16-YC17. ZmNF-YB16 interacted with ZmNF-YC17 via its histone fold domain to form a heterodimer in the cytoplasm and then entered the nucleus to form a heterotrimer with ZmNF-YA1 or ZmNF-YA7 under osmotic stress. Overexpression of ZmNF-YA1 improved drought and salt stress tolerance and root development of maize, whereas zmnf-ya1 mutants exhibited drought and salt stress sensitivity. ZmNF-YA1-mediated transcriptional regulation, especially in JA signaling, histone modification, and chromatin remodeling, could underlie the altered stress tolerance of zmnf-ya1 mutant plants. ZmNF-YA1 bound to promoter CCAAT motifs and directly regulated the expression of multiple genes that play important roles in stress responses and plant development. Comparison of ZmNF-YB16- and ZmNF-YA1-regulated genes showed that ZmNF-YA1 and ZmNF-YB16 have similar biological functions in stress responses but varied functions in other biological processes. Taken together, ZmNF-YA1 is a positive regulator of plant drought and salt stress responses and is involved in the root development of maize, and ZmNF-Y complexes with different subunits may have discrepant functions.
Rate and Predictors of Patients with Chronic Pain Establishing Care with Pain Psychology Following Pain Physician Referral
Authors: Lyon Ronit Y , Schuster Nathaniel M
Published: July 2022

Objective

To determine, among patients with chronic pain who had received pain physician referral to pain psychology, the rate of establishing care and factors related to establishing care with pain psychology.

Design

Retrospective study.

Setting

Academic tertiary care center.

Subjects

Patients from the University of California, San Diego (UCSD) Center for Pain Medicine.

Methods

This was an institutional review board–approved, retrospective study of 150 consecutive referrals of unique patients from UCSD Pain Medicine to UCSD Pain Psychology.

Results

Of 150 patients referred to pain psychology, 74 (49.3%) established care with pain psychology. Of 98 patients who had previously seen mental health services, 58 established care with pain psychology (59.2%; 95% confidence interval [CI]: 49% to 69%), whereas of 52 patients who had not previously seen mental health services, 16 established care with pain psychology (30.8%; 95% CI: 18% to 43%) (odds ratio [OR] 3.26; 95% CI: 1.60 to 6.66). In the patient subset with depression and/or anxiety, of 82 patients who had previously seen mental health services, 47 established care with pain psychology (57.3%; 95% CI: 47% to 68%), whereas of 20 patients who had not previously seen mental health services, three established care with pain psychology (15%; 95% CI: –1% to 31%) (OR 7.61; 95% CI: 2.07 to 28.01). Of 96 patients referred for general pain psychology evaluations, 43 established care (45%; 95% CI: 35% to 55%), whereas of 38 patients referred for preprocedural evaluation for an implantable device, 24 established care (63%; 95% CI: 48% to 78%).

Conclusion

Patients are significantly more likely to establish care with pain psychology if they have previously seen a mental health professional. This was even more marked among the patient subset with a history of depression and/or anxiety who had engaged in mental health services than among those with a history of depression and/or anxiety who had not engaged in mental health services. Whether referral was for general psychological evaluation or preprocedural evaluation for an implantable device did not significantly influence whether patients established care. Targeted interventions are needed to improve the likelihood of patients engaging with pain psychology services.
Autologous stem cell transplantation improves cardiopulmonary exercise testing outcomes in systemic sclerosis patients
Authors: Gadioli Leonardo Pippa , Costa-Pereira Karla , Dias Juliana B E , Moraes Daniela A , Crescêncio Júlio C , Schwartzmann Pedro V , Gallo-Júnior Lourenço , Schmidt André , Oliveira Maria Carolina
Published: July 2022

Objectives

Autologous haematopoietic stem cell transplantation (AHSCT) is a disease-modifying treatment for patients with severe SSc. Here, we aimed at assessing cardiopulmonary function outcomes of SSc patients after AHSCT.

Methods

Twenty-seven SSc adult patients treated with AHSCT were included in this retrospective study. Most had the diffuse cutaneous subset (93%) and pulmonary involvement (85%). Before and 12 months after AHSCT, patients underwent cardiopulmonary exercise testing, transthoracic echocardiography, pulmonary function test with diffusing capacity for carbon monoxide (DLCO), 6-min walk test (6MWT) and quality of life evaluations.

Results

After AHSCT, the peak VO2 increased from 954 to 1029 ml/min (P = 0.02), the percentage of predicted peak VO2 increased from 48.9 to 53.5 m (P = 0.01), and the distance measured by the 6MWT increased from 445 to 502 m (P = 0.01), compared with baseline. Improvements in peak VO2 correlated positively with improvements in 6MWT distance, and negatively with a decrease in resting heart rate. At baseline, patients with DLCO >70% had higher peak VO2 values than those with DLCO <70% (P = 0.04), but after AHSCT all patients showed improved VO2 values, regardless of baseline DLCO levels. Increases in VO2 levels after AHSCT positively correlated with increases in the physical component scores of the Short Form-36 quality of life questionnaire (r = 0.70; P = 0.0003).

Conclusion

AHSCT improves the aerobic capacity of SSc patients probably reflecting combined increments in lungs, skeletal muscle and cardiac function.
Evidence of subclinical atherosclerosis in eosinophilic granulomatosis with polyangiitis
Authors: Bello Federica , Bettiol Alessandra , Silvestri Elena , Mattioli Irene , Urban Maria Letizia , Palermo Adalgisa , Mazzetti Matteo , Malandrino Danilo , Calcaterra Ilenia , Vaglio Augusto , Di Minno Matteo Nicola Dario , Emmi Giacomo , Prisco Domenico
Published: July 2022

Objectives

Patients affected by eosinophilic granulomatosis with polyangiitis (EGPA) display an increased risk of atherothrombotic events compared with the general population. An increased frequency of subclinical markers of atherosclerosis has been observed in other ANCA-associated vasculitis, but no specific study focused on EGPA. We therefore evaluated subclinical atherosclerosis in EGPA patients and in a control population.

Methods

Forty EGPA patients and 80 controls matched by age, sex and traditional cardiovascular risk factors underwent sonographic assessment of common carotid artery (CCA) intima–media thickness (IMT). The presence of plaques of the CCA was also investigated. The correlation between CCA-IMT and clinical and laboratory features was also assessed.

Results

Median CCA-IMT was significantly higher in EGPA patients compared with controls (P = 0.002). Also, the proportion of subjects with increased CCA-IMT and with presence of plaques was significantly higher among EGPA patients (P < 0.001 for both). Moreover, within the EGPA cohort, CCA-IMT tended to increase with disease duration (P = 0.034) and corticosteroid cumulative dose (P = 0.004). No significant associations were found between CCA-IMT, ANCA status, other clinical features and therapeutic regimens. Notably, the prevalence of traditional cardiovascular risk factors was comparable in patients with vs without an increased CCA-IMT.

Conclusion

Ultrasound markers of subclinical atherosclerosis are increased in EGPA patients as compared with controls, independently of traditional cardiovascular risk factors.
A Sustainable Capital Asset Pricing Model (S-CAPM): Evidence from Environmental Integration and Sin Stock Exclusion
Authors: Zerbib Olivier David
Published: July 2022

This article shows how sustainable investing—through the joint practice of exclusionary screening and environmental, social, and governance (ESG) integration—affects asset returns. I develop an asset pricing model with partial segmentation and heterogeneous preferences. I characterize two exclusion premia generalizing Merton’s (1987) premium on neglected stocks and a taste premium that clarifies the relationship between ESG and financial performance. Focusing on US stocks, I estimate the model by applying it to sin stocks as excluded assets and using the holdings of green funds to proxy for environmental integration. The average annual exclusion effect is 2.79% for the period 1999–2019. Although the annual taste effect ranges from –1.12% to + 0.14% across industries for 2007–19, the taste effect spread between the top and bottom terciles of companies within each industry can exceed 2% per year. Finally, I estimate and explain the dynamics of these premia.
Proteomic biomarkers of Kleine–Levin syndrome
Authors: Hédou Julien , Cederberg Katie L , Ambati Aditya , Lin Ling , Farber Neal , Dauvilliers Yves , Quadri Mohammed , Bourgin Patrice , Plazzi Giuseppe , Andlauer Olivier , Hong Seung-Chul , Huang Yu-Shu , Leu-Semenescu Smaranda , Arnulf Isabelle , Taheri Shahrad , Mignot Emmanuel
Published: July 2022

Study Objectives

Kleine–Levin syndrome (KLS) is characterized by relapsing–remitting episodes of hypersomnia, cognitive impairment, and behavioral disturbances. We quantified cerebrospinal fluid (CSF) and serum proteins in KLS cases and controls.

Methods

SomaScan was used to profile 1133 CSF proteins in 30 KLS cases and 134 controls, while 1109 serum proteins were profiled in serum from 26 cases and 65 controls. CSF and serum proteins were both measured in seven cases. Univariate and multivariate analyses were used to find differentially expressed proteins (DEPs). Pathway and tissue enrichment analyses (TEAs) were performed on DEPs.

Results

Univariate analyses found 28 and 141 proteins differentially expressed in CSF and serum, respectively (false discovery rate <0.1%). Upregulated CSF proteins included IL-34, IL-27, TGF-b, IGF-1, and osteonectin, while DKK4 and vWF were downregulated. Pathway analyses revealed microglial alterations and disrupted blood–brain barrier permeability. Serum profiles show upregulation of Src-family kinases (SFKs), proteins implicated in cellular growth, motility, and activation. TEA analysis of up- and downregulated proteins revealed changes in brain proteins (p < 6 × 10−5), notably from the pons, medulla, and midbrain. A multivariate machine-learning classifier performed robustly, achieving a receiver operating curve area under the curve of 0.90 (95% confidence interval [CI] = 0.78–1.0, p = 0.0006) in CSF and 1.0 (95% CI = 1.0–1.0, p = 0.0002) in serum in validation cohorts, with some commonality across tissues, as the model trained on serum sample also discriminated CSF samples of controls versus KLS cases.

Conclusions

Our study identifies proteomic KLS biomarkers with diagnostic potential and provides insight into biological mechanisms that will guide future research in KLS.
Beef Quality Assurance national rancher survey: program participation, best management practices, and motivations for joining future sustainability programs
Authors: Klopatek S C , Cantwell A M , Roche L , Stackhouse-Lawson K , Oltjen J W
Published: July 2022

Till date, with over 137,000 certified members, the most successful rancher educational program has been the Beef Quality Assurance (BQA) program. The BQA program was established in the mid-1990’s to improve animal health and welfare with a primary objective to reduce the incidence of injection site lesions by instructing producers to administer injections in the neck only. The present study investigated the drivers of this success to inform future rancher education programs around agricultural sustainability. An online multistate survey was administered to cattle ranchers in collaboration with state cattlemen’s associations to better understand rancher motivations for adopting new practices and to gain insight on current involvement in BQA. In total, the survey consisted of 45 questions and was divided into 3 sections: (1) rancher demographics, (2) BQA participation and current best management practice (BMP) application, and (3) willingness to join new rancher educational programs. Data from 842 respondents are including in this study. Of the survey participants, 70% were currently BQA certified or had been BQA certified at one time, and 30% had never been certified. Ranchers who were BQA certified at any time were less likely to administer injections in areas other than the neck compared to ranchers who were not certified (P < 0.05), demonstrating the effectiveness of the BQA program. More than 80% of survey respondents who joined the BQA program stated they believed the BQA program improved animal health and welfare on their operation (n = 617). Among those who had not joined the BQA program, 40% believed BQA practices did not align with their ranching operation, while 38% had not heard of the BQA program (n = 256). The survey indicated that male ranchers, those with more years ranching, those with a larger percent of income coming from ranching, and ranches with larger total acres grazed were more likely to be BQA certified at any time (P < 0.05). Finally, ranchers who were BQA certified at any time were more likely to state that joining a rancher sustainability program would be beneficial to their operation. In conclusion, not only did the survey provide valuable insight into BQA program adoption but highlighted how BQA pedagogy and program structure may be a suitable framework for creating future rancher sustainability programs.
Orthotic hip brace as an alternative for treatment of femoral fractures in children under the age of 3 years: a retrospective study
Authors: Gross Itai , Hashavya Saar , Rogachev Sonia , Simanovsky Naum , Shrabaty Tareq , Zaidman Michael , Goldman Vladimir
Published: July 2022

Femoral fractures are among the most common reasons for orthopedic-related hospital admissions in children. While spica cast is recommended for most children younger than 5 years, in the last decades, Pavlik harness was proven to be a safe alternative for young children. The objective is to assess the safety, outcomes and complications of a hip abduction brace (HAB) for the treatment of femoral fractures in children under the age of 3 years. This 7-year retrospective study was conducted in a single tertiary hospital. Children aged 6–36 months diagnosed with a femoral fracture, which did not necessitate operative treatment, were included. HAB has been used as the treatment of choice for nondisplaced or minimally displaced fractures of the proximal femur as well as for both displaced and nondisplaced femoral shaft fractures. The database was composed of a total of 102 children under the age of 3 with femoral fractures. Twenty-nine (28.4%) patients were treated with HAB and the others with a spica cast. The average age (±SD) at presentation was 21.5 ± 6.1 months. The length of stay was 0.96 ± 1 day. The complication rate was 6.9%. A satisfactory outcome in terms of fracture alignment and union was reported in 100% of the patients treated with HAB. When compared with patients treated with a spica cast, the HAB group were younger, had less severe injuries, shorter lengths of stay, lower complication rates and no need for surgical intervention. HAB can be considered a safe and comfortable alternative in selected children aged 6–36 months with nondisplaced/mildly displaced proximal and diaphyseal femoral fractures.
A randomized controlled trial to evaluate efficacy and safety of early conversion to a low-dose calcineurin inhibitor combined with sirolimus in renal transplant patients
Authors: Zheng Xiang , Zhang Weijie , Zhou Hua , Cao Ronghua , Shou Zhangfei , Zhang Shuwei , Cheng Ying , Chen Xuchun , Ding Chenguang , Tang Zuofu , Li Ning , Shi Shaohua , Zhou Qiang , Chen Qiuyuan , Chen Gang , Chen Zheng , Zhou Peijun , Hu Xiaopeng , Zhang Xiaodong , Na Ning , Wang Wei
Published: July 2022

Background:

The calcineurin inhibitor (CNI)-based immune maintenance regimen that is commonly used after renal transplantation has greatly improved early graft survival after transplantation; however, the long-term prognosis of grafts has not been significantly improved. The nephrotoxicity of CNI drugs is one of the main risk factors for the poor long-term prognosis of grafts. Sirolimus (SRL) has been employed as an immunosuppressant in clinical practice for over 20 years and has been found to have no nephrotoxic effects on grafts. Presently, the regimen and timing of SRL application after renal transplantation vary, and clinical data are scarce. Multicenter prospective randomized controlled studies are particularly rare. This study aims to investigate the effects of early conversion to a low-dose CNI combined with SRL on the long-term prognosis of renal transplantation.

Methods:

Patients who receive four weeks of a standard regimen with CNI + mycophenolic acid (MPA) + glucocorticoid after renal transplantation in multiple transplant centers across China will be included in this study. At week 5, after the operation, patients in the experimental group will receive an additional administration of SRL, a reduction in the CNI drug doses, withdrawal of MPA medication, and maintenance of glucocorticoids. In addition, patients in the control group will receive the maintained standard of care. The patients’ vital signs, routine blood tests, routine urine tests, blood biochemistry, serum creatinine, BK virus (BKV)/ cytomegalovirus (CMV), and trough concentrations of CNI drugs and SRL at the baseline and weeks 12, 24, 36, 48, 72, and 104 after conversion will be recorded. Patient survival, graft survival, and estimated glomerular filtration rate will be calculated, and concomitant medications and adverse events will also be recorded.

Conclusion:

The study data will be utilized to evaluate the efficacy and safety of early conversion to low-dose CNIs combined with SRL in renal transplant patients.

Trial registration:

Chinese Clinical Trial Registry, ChiCTR1800017277.
The Impact of Combined Oral Contraceptives on Adolescents with Macromastia
Authors: Nuzzi Laura C. , Pramanick Tannishtha , Massey Gabrielle G. , Walsh Landis R. , McNamara Catherine T. , Firriolo Joseph M. , DiVasta Amy D. , Labow Brian I.
Published: July 2022

Background:

The combined oral contraceptive pill (COC), containing both estrogen and progestin, is commonly prescribed to adolescents for numerous health benefits. However, there is concern among patients and providers that its use may exacerbate breast growth. This retrospective, case-control study examined the association between COC use and macromastia-related breast hypertrophy and symptomatology in adolescents.

Methods:

A total of 378 patients undergoing reduction mammaplasty between the ages of 12-21 years were assessed for baseline and postoperative breast symptomatology and COC use. Additionally, the medical records of 378 female controls of the same age range were retrospectively reviewed.

Results:

Although a lower proportion of the macromastia cohort used any hormonal contraception compared to controls (37.8% vs 64.8%; odds ratio, 0.33; 95% confidence interval, 0.24-0.44; P < .001), they were more often prescribed COCs (82.5% vs 52.7%; odds ratio, 1.93; 95% confidence interval, 1.29-2.68; P < .001). Participants with macromastia who used COCs had a smaller median normalized amount of breast tissue resected during reduction mammaplasty than those who never used hormonal contraception (639.5 g/m2 vs 735.9 g/m2
; P = .003). COCs were not associated with breast-related symptomology or clinical impairment, or postoperative breast growth (P > .05, all).

Conclusions:

COC use during adolescence may be associated with developing less severe breast hypertrophy. COCs do not appear to exacerbate macromastia-related symptomatology or impact postoperative growth in young women following reduction mammaplasty. Although additional research is needed, providers are encouraged to consider COCs for their patients with macromastia when indicated and appropriate.
A Statistical Analysis of The Effects of Comorbidities on the Inferior Pedicle Reduction Mammaplasty; Are there premorbid conditions which prohibit this procedure?
Authors: Friedman Harold , Schlub Riley , Durkin Martin , Clark Emily , Gilstrap Jarom , McGreevy Donna
Published: July 2022

Background:

Multiple studies have analyzed the impact of co-morbidities on breast reduction surgery with mixed results. The purpose of this investigation was to perform a statistical analysis of all complications by a single surgeon, using a single technique for breast reduction

Methods:

Records of patients undergoing breast reduction from 1984 to 2019 with an inferior pedicle were reviewed. Co-morbidities analyzed included hypertension, diabetes, nicotine use, weight of breast tissue resected, pedicle length and basal metabolic index. The literature on the effects of comorbidities on outcomes for breast reconstruction were also reviewed.

Results:

Although increasing BMI significantly increased the rate of fat necrosis, it did not impact those patients requiring reoperation for this complication. BMI greater than 35, weight of tissue resection greater than 1000gm, and nipple to inframammary fold distance greater than 20cm all increased the odds ratio of having a breast with some fat necrosis. Increasing BMI increased the risk of wound healing problems (both major and minor), but not for patients requiring reoperation. BMI greater than 35, breast tissue resection greater than 1000gm, and nipple to fold distance greater than 20 only minimally increased the odds ratio for a major wound complication.

Conclusions:

Patients with increased BMI are at greater risk for fat necrosis and wound healing complications. However, these usually can be managed conservatively in patients undergoing inferior pedicle breast reduction. Patients do not require free nipple grafting. The use of nicotine, presence of diabetes or hypertension does not impact outcome.
Picking the Right Plane: A Comparison of Total Submuscular, Dual-Plane, and Prepectoral Implant-based Breast Reconstruction
Authors: Bekisz Jonathan M , Salibian Ara A , Frey Jordan D , Choi Mihye , Karp Nolan S
Published: July 2022

Background:

Implant-based breast reconstruction has evolved, with a recent resurgence of prepectoral techniques. Comparative reconstructive outcomes and complications have not been fully elucidated among the total submuscular (TSM), dual-plane (DP), and prepectoral planes of implant placement.

Methods:

All immediate implant-based breast reconstructions from March 2017 through August 2019 were retrospectively reviewed. Cases were divided into TSM, DP, and prepectoral cohorts. Demographics, operative techniques, and reconstructive outcomes and complications were compared among groups.

Results:

826 cases (510 patients) were identified and divided into TSM (n=392), DP (n=358), and prepectoral (n=76) cohorts. Average follow-up for all patients was 27 months. The prepectoral cohort had a higher average BMI and rate of prior reduction/mastopexy. Overall complications were lowest in the TSM group, though this difference was not statistically significant. Major infection occurred more frequently in the DP group compared to the TSM cohort. The prepectoral cohort had a significantly increased incidence of wound dehiscence than the TSM group, while both the dual-plane and prepectoral groups had higher rates of seroma formation and explantation compared to TSM.

Conclusions:

Overall reconstructive complication rates were comparable among the cohorts. Compared to those undergoing TSM reconstruction, the DP cohort was more likely to develop a major infection or require explantation, while the prepectoral group had significantly higher rates of isolated dehiscence, seroma formation, and explantation. This suggest that the absence of overlying vascularized muscle may lead to an inherent inability to tolerate wound healing complications, though further research is needed to clarify these observations.
The Thoracodorsal Artery Perforator Flap: a Powerful Tool in Breast Reconstruction.
Authors: Homsy Christopher , Theunissen Taylor , Sadeghi Alireza
Published: July 2022

Background:

The use of perforator-based flaps in breast cancer reconstruction has evolved significantly and surgical techniques have undergone major refinements in the last thirty years, making them the flaps of choice in autologous breast reconstruction. However, flap complications may lead to significant breast shape deformity and significant patient dissatisfaction. Restoring breast contour may therefore require multiple revision procedures.

In this study our objective was to review our experience and evaluate the outcomes of the thoracodorsal artery perforator (TDAP) flap in breast reconstruction.

Methods:

We conducted a retrospective chart review of all women undergoing breast reconstruction between 2012 and 2018. Inclusion criteria were patients who underwent a mastectomy (unilateral or bilateral) with immediate or requiring a revision reconstruction with TDAP. Patients with breast reconstruction for non-malignant etiologies were excluded from the study. Patient demographics, risk factors, indications, operative details, complications were extracted from medical records. Complications were divided into major (partial or total flap necrosis, hematoma, and wound breakdown requiring operative management) and minor complications (cellulitis, seroma, minor wound breakdown managed with local wound care).

Results:

One-hundred and thirty-eight charts were reviewed between the years 2012 and 2018. One-hundred and twenty-six patients met the inclusion criteria. Mean age was 52.1. Mean body mass index (BMI) was 29.1. A total of 174 TDAP flaps were performed: 171 pedicled and 3 free flaps. The success rate was 98.3%. There were 3 flap losses (all partial). Operable fat necrosis rate was 3%. Donor-site morbidity was low, accounting for a rate of only 1.2%. There was no difference in complication rate between patients who had a history of radiation to those who did not (16.7% vs. 18.6% respectively; p=0.829).

Conclusion:

Our study is the largest series in the literature that highlights the utility of the TDAP flap in breast reconstruction. The thoracodorsal artery perforator flap is a reproducible and reliable reconstructive tool that may be used to reconstruct breast deformities acquired from wound complications following both implant-based and autologous breast reconstructions. It is a powerful flap that should be considered particularly in patients in whom other major reconstructive options were exhausted or unavailable.
Robotic Distal Pancreatectomy
Authors: Müller Philip C. , Breuer Eva , Nickel Felix , Zani Sabino , Kauffmann Emanuele , De Franco Lorenzo , Tschuor Christoph , Krohn Paul Suno , Burgdorf Stefan K. , Jonas Jan Philipp , Oberkofler Christian E. , Petrowsky Henrik , Saint-Marc Olivier , Seelen Leonard , Molenaar Izaak Quintus , Wellner Ulrich , Keck Tobias , Coratti Andrea , van Dam Jacob L. , de Wilde Roeland , Koerkamp Bas Groot , Valle Valentina , Giulianotti Pier , Ghabi Elie , Moskal David , Lavu Harish , Vrochides Dionisios , Martinie John , Yeo Charles , Sánchez-Velázquez Patricia , Ielpo Benedetto , Ajay Pranay S. , Shah Mihir M. , Kooby David A. , Gao Song , Hao Jihui , He Jin , Boggi Ugo , Hackert Thilo , Allen Peter , Borel-Rinkes Inne H.M. , Clavien Pierre Alain
Published: July 2022

Background and Objective:

Robotic distal pancreatectomy (DP) is an emerging attractive approach, but its role compared with laparoscopic or open surgery remains unclear. Benchmark values are novel and objective tools for such comparisons. The aim of this study was to identify benchmark cutoffs for many outcome parameters for DP with or without splenectomy beyond the learning curve.

Methods:

This study analyzed outcomes from international expert centers from patients undergoing robotic DP for malignant or benign lesions. After excluding the first 10 cases in each center to reduce the effect of the learning curve, consecutive patients were included from the start of robotic DP up to June 2020. Benchmark patients had no significant comorbidities. Benchmark cutoff values were derived from the 75th or the 25th percentile of the median values of all benchmark centers. Benchmark values were compared with a laparoscopic control group from 4 high-volume centers and published open DP landmark series.

Results:

Sixteen centers contributed 755 cases, whereof 345 benchmark patients (46%) were included the analysis. Benchmark cutoffs included: operation time ≤300 minutes, conversion rate ≤3%, clinically relevant postoperative pancreatic fistula ≤32%, 3 months major complication rate ≤26.7%, and lymph node retrieval ≥9. The comprehensive complication index at 3 months was ≤8.7 without deterioration thereafter. Compared with robotic DP, laparoscopy had significantly higher conversion rates (5×) and overall complications, while open DP was associated with more blood loss and longer hospital stay.

Conclusion:

This first benchmark study demonstrates that robotic DP provides superior postoperative outcomes compared with laparoscopic and open DP. Robotic DP may be expected to become the approach of choice in minimally invasive DP.
Using real world data to advance the provision of supportive cancer care: mucositis as a case study
Authors: Wardill Hannah R. , Sonis Steve T. , Blijlevens Nicole M.A.
Published: July 2022

Purpose of review

For decades, clinical decision making and practice has been largely informed by data generated through randomized clinical trials (RCTs). By design, RCTs are highly restricted in both scope and scale, resulting in narrow indications and iterative advances in clinical practice. With the transition to electronic health records, there are now endless opportunities to utilize these ‘real world’ data (RWD) to make more substantive advances in our understanding that are, by nature, more applicable to reality. This review discusses the current paradigm of using big data to advance and inform the provision of supportive cancer care, using mucositis as a case study.

Recent findings

Global efforts to synthesize RWD in cancer have almost exclusively focused on tumor classification and treatment efficacy, leveraging on routine tumor pathology and binary response outcomes. In contrast, clinical notes and billing codes are not as applicable to treatment side effects which require integration of both clinical and biological data, as well as patient-reported outcomes.

Cancer treatment-induced toxicities are heterogeneous and complex, and as such, the use of RWD to better understand their etiology and interaction is challenging. Multidisciplinary cooperation and leadership are needed to improve data collection and governance to ensure the right data is accessible and reliable.
Moniliella aeria sp. nov., a novel yeast isolated from the air of a Wuliangye baijiu-making workshop
Authors: Lei Xuejun , Zheng Jia , Zhao Dong , Qiao Zongwei , An Mingzhe , Zhang Xia
Published: July 2022

During an investigation of the diversity of airborne yeasts in a famous Chinese baijiu fermentation workshop, two yeast strains were isolated from the air of the Wuliangye 501# baijiu-making workshop in Yibin, Sichuan Province, PR China and subjected to taxonomic analysis. The results of phylogenetic analysis of two regions of the rRNA gene cluster, the D1/D2 domains of the large subunit (LSU) rRNA gene and the internal transcribed spacer (ITS) region, indicated that these strains represented a novel species of the genus Moniliella distinct from closely related species. The similarity between the novel species and the most closely related known species, Moniliella dehoogii, was 94.1 % for the D1/D2 LSU rRNA gene (30 substitutions and 12 indels out of 556 bp) and 95.6 % for the ITS region (9 substitutions and 6 indels out of 475 bp). In contrast with M. dehoogii, this novel species was able to assimilate d-ribose, l-arabinose, d-arabinose, cellobiose, d-glucono-1,5-lactone, dl-lactate, citrate, 1,2-propanediol, 2,3-butanediol and ethanol but was unable to ferment raffinose or assimilate inulin. On the basis of the results of phylogenetic analysis and the physiological characteristics, these investigated strains represent a novel species of the genus Moniliella, for which the name Moniliella aeria sp. nov. is proposed. Its holotype is CGMCC 20235T, and the MycoBank number is MB840188.
Perioperative changes in oxygen consumption: estimations from minimal-invasive cardiac output and a-cvO2difference parallel to indirect calorimetry
Authors: Jakobsson Julia , Norén Carl , Hagel Eva , Backheden Magnus , Kalman Sigridur , Bartha Erzsébet
Published: July 2022

Feasible estimations of perioperative changes in oxygen consumption could enable larger studies of its role in postoperative outcomes. Current methods, by pulmonary artery catheterisation or breathing gas analysis, are often regarded as either invasive or technically requiring. In this pilot study, we investigated the relationship between estimations of oxygen consumption, based on minimal-invasive cardiac output and arterial-central venous blood gas sampling, and indirect calorimetry in the perioperative period using the data collected during a clinical trial on perioperative oxygen transport.

In 20 patients >65 years during epidural and general anaesthesia for open abdominal surgery, Fick-based estimations of oxygen consumption(EVO2), the product of cardiac output from LiDCO™plus(LiDCO Ltd, Cambridge, UK) and arterial-central venous oxygen content difference, were compared with indirect calorimetry(GVO2) using QuarkRMR(COSMED, srl. Italy). Eighty-five simultaneous intra- and postoperative measurements at different time-points were analysed for prediction, parallelity and by traditional agreement assessment. There was an overall association between GVO2and EVO2, 73(95% CI 62 to 83) + 0.45(95% CI 0.29 to 0.61) EVO2ml min-1m-2,P<0.0001. GVO2and EVO2changed in parallel intra- and postoperatively when normalised to their respective overall means. Unadjusted mean difference between GVO2and EVO2indexed for body surface area was 26(95% CI 20 to 32) with limits of agreement (1.96SD) of -32 to 85 ml min-1m-2and did not change over time. There was low correlation for absolute agreement, ICC(A,1) 0.37(95% CI 0.34 to 0.65) [F(84,10.2)=3.07,P=0.0266].

Despite lack of absolute agreement, the estimated oxygen consumption changed in parallel to the metabolic measurements in the perioperative period. Prediction or trending of oxygen consumption by this or similar methods could be further evaluated in larger samples.
A Mixed Methods Approach Incorporating Text Analytics to Examine Persistence of Depression
Authors: Johnson Sarah A. , Cassells Andrea , Lin T.J. , Weiss Elisa S. , Tobin Jonathan N.
Published: July 2022

Background

Some patients’ depression persists despite evidence-based interventions; understanding factors associated with depression persistence could inform screening and treatment. We used a novel mixed-methods approach to examine demographic, clinical, and social factors affecting depression persistence among older, low-income women; we also assessed the utility of this approach for evaluating intervention fidelity.

Methods

Data used for this study were generated from a comparative effectiveness study comparing the impact of prevention care management (PCM) versus a collaborative care intervention (CCI) on depression among women overdue for cancer screening: We reviewed 700 care manager logs to identify themes among patients’ experiences and analyzed language use using NVivo®’s natural language processing (NLP) functionality. 757 women age 50-64 who screened positive for depression at baseline using the Patient Health Questionnaire (PHQ)-9 and were overdue for ≥1 cancer screening test (breast, cervical, and/or colorectal) participated. All received primary care in XXX Federally Qualified Health Centers. We used NLP to quantify differences in language use across intervention groups and explored how often themes appeared in logs of participants whose depression did not meaningfully improve based on PHQ-9 scores. Differences in demographic, clinical, and social factors were examined.

Results

Participants with persistent depression were more likely to discuss pain, fear, and transportation. Asthma and anxiety were associated with lower likelihood of depression remission, while no differences were observed in depression remission rates among those with diabetes or hypertension. Patient-centered words, including “needs” and “feelings”, were more common in the CCI group, while procedure-related words, like “screening” and “mammography”, appeared more frequently in the PCM group.

Conclusions

Patient-related factors and social barriers contributed to depression persistence. NLP identified patterns of language use in case logs, suggesting unmet needs among depressed patients. NLP is an efficient, effective method for identifying themes in unstructured text and monitoring intervention fidelity.
Contrasting and conserved roles of NPR pathways in diverged land plant lineages
Authors: Jeon Hyung-Woo , Iwakawa Hidekazu , Naramoto Satoshi , Herrfurth Cornelia , Gutsche Nora , Schlüter Titus , Kyozuka Junko , Miyauchi Shingo , Feussner Ivo , Zachgo Sabine , Nakagami Hirofumi
Published: July 2022

The NPR proteins function as salicylic acid (SA) receptors inArabidopsis thaliana. AtNPR1 plays a central role in SA-induced transcriptional reprogramming whereby positively regulates SA-mediated defense. NPRs are found in the genomes of nearly all land plants. However, we know little about the molecular functions and physiological roles of NPRs in most plant species. Our phylogenetic and alignment analyses show that Brassicaceae NPR1-like proteins have characteristically gained or lost functional residues or motifs identified in AtNPRs, pointing to the possibility of a unique evolutionary trajectory for the Brassicaceae NPR1-like proteins that has resulted in peculiar functions. In line with this observation, we find that the only NPR inMarchantia polymorpha, MpNPR, is not the master regulator of SA-induced transcriptional reprogramming and negatively regulates bacterial resistance in this species. Interspecies complementation analysis indicated that the molecular properties of AtNPR1 and MpNPR are partially conserved, implying the diversification of NPR-associated pathways contributed to distinct roles of NPR in different species. The Mpnprtranscriptome suggested potential roles of MpNPR in heat and far-red light responses. We identify both Mpnprand Atnpr1-1display enhanced thermomorphogenesis. NPRs and NPR-associated pathways clearly have evolved distinctively in diverged land plant lineages to cope with different terrestrial environments.
Leaf trichome diversity, acylsugar concentration, and their relationships to leaf area inSolanum galapagense
Authors: Henzler Ilan , Khazaei Hamid
Published: July 2022

Glandular trichomes are physical and chemical barriers used by some tomato wild relatives to confer resistance against insect pests and diseases transmitted by them.Solanum galapagensehas been identified as one of the potential sources of insect pest resistance. The present study aimed to examine the trichome diversity and acylsugar concentration of 26 accessions ofS. galapagensealong with one cultivated tomato (S. lycopersicum) and one cherry tomato (S. l. cerasiforme) cultivar. The results revealed large genetic variation amongS. galapagenseaccessions for all studied traits. TheS. galapagenseaccessions had significantly higher trichome types IV on the adaxial and abaxial surfaces of the leaf and greater acylsugar concentration but smaller leaflet area than cultivated tomato. The selected cherry tomato line represents greater trichome type IV and acylsugar than other groups. The acylsugar concentration was positively associated with trichome type IV but negatively associated with trichome type V on both leaf surfaces. Leaflet area was negatively associated with trichome IV density and acylsugar concentration. Analysis of DNA markers revealed the presence of two previously identified whitefly-resistance alleles inS. galapagenseaccessions. This study will support breeding programs aiming to improve insect pest resistance in tomato cultivars using crop wild relatives.
Inference of selective sweep parameters through supervised learning
Authors: Caldas Ian V. , Clark Andrew G. , Messer Philipp W.
Published: July 2022

A selective sweep occurs when positive selection drives an initially rare allele to high population frequency. In nature, the precise parameters of a sweep are seldom known: How strong was positive selection? Did the sweep involve only a single adaptive allele (hard sweep) or were multiple adaptive alleles at the locus sweeping at the same time (soft sweep)? If the sweep was soft, did these alleles originate from recurrent new mutations (RNM) or from standing genetic variation (SGV)? Here, we present a method based on supervised machine learning to infer such parameters from the patterns of genetic variation observed around a given sweep locus. Our method is trained on sweep data simulated with SLiM, a fast and flexible framework that allows us to generate training data across a wide spectrum of evolutionary scenarios and can be tailored towards the specific population of interest. Inferences are based on summary statistics describing patterns of nucleotide diversity, haplotype structure, and linkage disequilibrium, which are estimated across systematically varying genomic window sizes to capture sweeps across a wide range of selection strengths. We show that our method can accurately infer selection coefficients in the range 0.01 < s < 100 and classify sweep types between hard sweeps, RNM soft sweeps, and SGV soft sweeps with accuracy 69 % to 95 % depending on sweep strength. We also show that the method infers the correct sweep types at three empirical loci known to be associated with the recent evolution of pesticide resistance in Drosophila melanogaster. Our study demonstrates the power of machine learning for inferring sweep parameters from present-day genotyping samples, opening the door to a better understanding of the modes of adaptive evolution in nature.

Author summary

Adaptation often involves the rapid spread of a beneficial genetic variant through the population in a process called a selective sweep. Here, we develop a method based on machine learning that can infer the strength of selection driving such a sweep, and distinguish whether it involved only a single adaptive variant (a so-called hard sweep) or several adaptive variants of independent origin that were simultaneously rising in frequency at the same genomic position (a so-called soft selective sweep). Our machine learning method is trained on simulated data and only requires data sampled from a single population at a single point in time. To address the challenge of simulating realistic datasets for training, we explore the behavior of the method under a variety of testing scenarios, including scenarios where the history of the population of interest was misspecified. Finally, to illustrate the accuracy of our method, we apply it to three known sweep loci that have contributed to the evolution of pesticide resistance in Drosophila melanogaster.
Cell-type-specific aberrant R-loop accumulation regulates target gene and confers cell-specificity
Authors: Pan Xingxin , Huang L. Frank
Published: July 2022

Aberrant R-loops have been found associated with diverse biological dysfunction, including cancers and neurological disorders. However, there isn’t any systematic research to characterize aberrant R-loops at the whole genome level at a large scale. Here, we identified aberrant R-loops, including proliferative and suppressive R-loops of 5’ end, body, 3’ end respectively for the first time, which are found prevalent and vary across diverse physiological conditions. After that, we proposed a deep neural network-based framework, named Deep R-looper Discriminant to identify aberrant R-loops against housekeeping R-loops. To evaluate the predictive performance of the deep learning framework, we constructed multiple prediction models as benchmarks and it showed our framework achieves robust performance for identifying aberrant R-loops against those normal R-loops. Furthermore, we found the customized Deep R-looper Discriminant was capable of distinguishing between proliferative and suppressive R-loops at 5’ end, body, 3’ end respectively, outperforming baselines. When inspecting the contribution of epigenetic marks to aberrant R-loops of each class, we inferred landmark epigenetic modifications which play a crucial role in the differentiated formation of those aberrant R-loops, and cell line specificity of epigenetic marks map was found as well. To explore the characteristics of these aberrant R-loops, we depicted the histone landscapes for aberrant R-loops. Finally, we integrated omics and identified target genes regulated directly by aberrant R-loops and found key transcription factors involved in R-loop regulation, which may be implicated in conferring cell-specificity and cancer development and progression.
Monitoring Non-Specific Adsorption at Solid-Liquid Interfaces by Supercritical Angle Fluorescence Microscopy
Authors: Au Aaron , Ho Man , Wheeler Aaron R. , Yip Christopher M.
Published: July 2022

Supercritical angle fluorescence (SAF) microscopy is a novel imaging tool based on the use of distance-dependent fluorophore emission patterns to provide accurate locations of fluorophores relative to a surface. This technique has been used extensively to construct accurate cellular images and to detect surface phenomena in a static environment. However, the capability of SAF microscopy in monitoring dynamic surface phenomena and changes in millisecond intervals is underexplored. Here we report on a hardware add-on for a conventional inverted microscope coupled with a post-processing Python module that extends the capability of SAF microscopy to monitor dynamic surface phenomena thereby greatly expanding the range of potential applications of this tool. We first assessed the performance of the system by probing the specific binding of biotin-fluorescein conjugates to a neutravidin-coated cover glass in the presence of non-binding fluorescein. The SAF emission was observed to increase with the quantity of bound fluorophore on the cover glass. However, high concentration of unbound fluorophore also contributed to overall SAF emission, leading to over-estimation in surface-bound fluorescence. To expand the applications of SAF in monitoring surface phenomena, we monitored the non-specific surface adsorption of BSA and non-ionic surfactants on a Teflon-AF surface. Solution mixtures of BSA and nine Pluronic/Tetronic surfactants were exposed to a Teflon-AF surface. No significant BSA adsorption was observed in all BSA-surfactant solution mixture with negligible SAF intensity. Finally, we monitored the adsorption dynamics of BSA onto the Teflon-AF surface and observed rapid BSA adsorption on Teflon-AF surface within 10 seconds of addition. The adsorption rate constant (ka) and half-life of BSA adsorption on Teflon-AF were determined to be 0.2093±0.002 s−1 and 3.312±0.032 s respectively using a pseudo-first-order adsorption equation.