bluuebunny/crossref_metadata_2025 huggingface dataset:
Three-dimensional-printed collagen/chitosan/secretome derived from HUCMSCs scaffolds for efficient neural network reconstruction in canines with traumatic brain injury
Authors: Liu Xiaoyin , Zhang Guijun , Wei Pan , Zhong Lin , Chen Yaxing , Zhang Jianyong , Chen Xuyi , Zhou Liangxue
Published: June 2022

The secretome secreted by stem cells and bioactive material has emerged as a promising therapeutic choice for traumatic brain injury (TBI). We aimed to determine the effect of 3D-printed collagen/chitosan/secretome derived from human umbilical cord blood mesenchymal stem cells scaffolds (3D-CC-ST) on the injured tissue regeneration process. 3D-CC-ST was performed using 3D printing technology at a low temperature (−20°C), and the physical properties and degeneration rate were measured. The utilization of low temperature contributed to a higher cytocompatibility of fabricating porous 3D architectures that provide a homogeneous distribution of cells. Immediately after the establishment of the canine TBI model, 3D-CC-ST and 3D-CC (3D-printed collagen/chitosan scaffolds) were implanted into the cavity of TBI. Following implantation of scaffolds, neurological examination and motor evoked potential detection were performed to analyze locomotor function recovery. Histological and immunofluorescence staining were performed to evaluate neuro-regeneration. The group treated with 3D-CC-ST had good performance of behavior functions. Implanting 3D-CC-ST significantly reduced the cavity area, facilitated the regeneration of nerve fibers and vessel reconstruction, and promoted endogenous neuronal differentiation and synapse formation after TBI. The implantation of 3D-CC-ST also markedly reduced cell apoptosis and regulated the level of systemic inflammatory factors after TBI.
Why do Big Science projects exist? The role of social preferences
Authors: Vincenzi Marco
Published: June 2022

Recent work has excluded sociocultural factors among the determinants of Big Science projects. This paper empirically tests the role of four different measures of social preferences, namely altruism, trust, negative reciprocity, and positive reciprocity, in increasing the likelihood of sustaining international cooperation in Big Science projects. Using a novel database of cross-sectional observations from seventy-six countries, this study finds evidence of a positive and statistically significant relationship between negative reciprocity and both time and risk preferences, namely patience and risk-taking. The science policy implication of this study is that a broader theory of clubs can guide meta-organizations in establishing, maintaining, or denying membership in Big Science projects based on the long-term orientation and reputation as a committed cooperator of a country.
Acetabular Reaming Is a Reliable Model to Produce and Characterize Periarticular Heterotopic Ossification of the Hip
Authors: Negri Stefano , Wang Yiyun , Li Zhao , Qin Qizhi , Lee Seungyong , Cherief Masnsen , Xu Jiajia , Hsu Ginny Ching-Yun , Tower Robert Joel , Presson Bradley , Levin Adam , McCarthy Edward , Levi Benjamin , James Aaron W
Published: June 2022

Heterotopic ossification (HO) is a pathologic process characterized by the formation of bone tissue in extraskeletal locations. The hip is a common location of HO, especially as a complication of arthroplasty. Here, we devise a first-of-its-kind mouse model of post-surgical hip HO and validate expected cell sources of HO using several HO progenitor cell reporter lines. To induce HO, an anterolateral surgical approach to the hip was used, followed by disclocation and acetabular reaming. Animals were analyzed with high-resolution roentgenograms and micro-computed tomography, conventional histology, immunohistochemistry, and assessments of fluorescent reporter activity. All the treated animals’ developed periarticular HO with an anatomical distribution similar to human patients after arthroplasty. Heterotopic bone was found in periosteal, inter/intramuscular, and intracapsular locations. Further, the use of either PDGFRα or scleraxis (Scx) reporter mice demonstrated that both cell types gave rise to periarticular HO in this model. In summary, acetabular reaming reproducibly induces periarticular HO in the mouse reproducing human disease, and with defined mesenchymal cellular contributors similar to other experimental HO models. This protocol may be used in the future for further detailing of the cellular and molecular mediators of post-surgical HO, as well as the screening of new therapies.
The Population of Fusarium oxysporum f. sp. cubense in Brazil Is Not Structured by Vegetative Compatibility Group or by Geographic Origin
Authors: Batista Izabel C. A. , Heck Daniel W. , Santos Alessandro , Alves Gabriel , Ferro Camila G. , Dita Miguel , Haddad Fernando , Michereff Sami J. , Correia Kamilla C. , da Silva Christiana F. B. , Mizubuti Eduardo S. G.
Published: June 2022

Fusarium wilt, caused by the soilborne fungus Fusarium oxysporum f. sp. cubense ( Foc), is considered one of the most destructive diseases of bananas in Brazil. In this study, a collection of 194 monosporic isolates from several banana-producing regions located in different climatic zones along a south-to-north transect in Brazil was formed to assess the genetic structure of the population of Foc. The isolates underwent pathogenicity tests, PCR diagnosis for the detection of tropical race 4, and screening of SIX homolog genes that produce putative effector proteins. The vegetative compatibility group (VCG) of 119 isolates was determined by pairing against 17 internationally known VCG-tester strains. A group of 158 isolates was selected for simple sequence repeat (SSR) genotyping. There was moderate diversity of Foc in Brazil. Eight VCGs were identified: 0120, 0122, 0124, 0125, 0128, 01215, 01220, and 01222, of which 78% of isolates belong to a single VCG, whereas 22% of isolates are assigned to multiple VCGs, belonging to complexes of VCGs. The distribution of VCGs is uneven and independent of the banana genotype. The isolates of a VCG shared a similar profile of SIX homologs, but there was no association with geographic region. Four SSR loci were polymorphic, and, on average, 7.5 alleles were detected per locus. Thirty-five multilocus genotypes (MLGs) were identified. There was no association between VCG and MLGs, and no genetic structure of the population of Foc in Brazil was detected.
The Divergence Between Hospital Charges and Reimbursements For Primary 1–2-level Lumbar Fusion Has Increased Over Time
Authors: Bogdan Paulina , Walocha Daniel , Gordon Adam M. , Lam Aaron , Ng Mitchell K. , Saleh Ahmed , Razi Afshin E.
Published: June 2022

Study Design:

A retrospective cohort study was performed for patients undergoing 1–2-level lumbar fusion (1–2LF) from 2005 to 2014 using an administrative claims database.

Objective:

The objective of this study was to determine changes in: (1) annual charges; (2) annual reimbursement rates; and (3) annual difference (charges minus reimbursements) in patients undergoing 1–2LF.

Summary of Background Data:

With implementation of value-based care in orthopaedics, coupled with the rise in number of patients undergoing 1–2LF, understanding the discordance in hospital charges and reimbursements is needed. The difference in hospital charges to reimbursements specifically for 1–2LF for degenerative disc disease has not been studied.

Materials and Methods:

A Medicare administrative claims database was queried for patients undergoing primary lumbar fusion using ICD-9 procedural code 81.04–81.08. Patients specifically undergoing 1–2LF were filtered from this cohort using ICD-9 procedural code 81.62. The query yielded 547,067 patients who underwent primary 1–2LF. Primary outcomes analyzed included trends in charges, reimbursement rates, and net difference in cost over time and per annual basis. Linear regression evaluated the change in costs over time with a P-value less than 0.05 considered significant.

Results:

From 2005 to 2014, total charges increased from $6,085,838,407 to $19,621,979,956 and total reimbursements increased from $1,677,764,831 to $4,656,702,685 (all P<0.001). Per patient charges increased 92.10% from 2005 to 2014 for patients undergoing primary 1–2LF from $129,992 to $249,697 (P<0.001). Similarly, an increase in reimbursement per patient of 65.35% from $35,836 to $59,258 (P<0.001) was noted. The annual difference in charges to reimbursements increased 102.26% during the study interval from $94,155 to $190,439 (P<0.001).

Conclusions:

Per patient charges and reimbursements both increased over the study period; however, charges increased 30% more than reimbursements. Further breakdown of hospital, surgeon, and anesthesiologist reimbursements for 1–2LF is needed.

Level of Evidence:

Level III.
Hem-o-lok-free and Retzius-sparing robot-assisted laparoscopic radical prostatectomy with retrograde release of the neurovascular bundle
Authors: Wang Yong , Liu Zihao , Huang Hua , Ma Yuan , Niu Yuanjie
Published: June 2022

Background:

Robot-assisted laparoscopic radical prostatectomy (RARP) has gradually become the standard surgical procedure for prostate cancer. This video, http://links.lww.com/CURRUROL/A10 aimed to demonstrate a new and improved surgical approach for prostate cancer that passes through the pouch of Douglas and allows retrograde release of the neurovascular bundle (NVB). The technique is Hem-o-lok-free and Retzius-sparing and is performed without opening the pelvic floor fascia during RARP.

Methods:

A 69-year-old man was diagnosed with prostate cancer (clinical stage T2bN0M0). We followed the process of Retzius-sparing RARP [published by Galfano et al. in 2013] and did some modification. The critical technical points associated with this technique included locating the fascial layer at the prostatic apex and performing complete retrograde release of the NVB along the anatomical structure. We used diathermy to perform precision hemostasis on large vessels, especially those around the basal part of prostate, with relatively less damage. In addition, Hem-o-lok was not used in this procedure.

Results:

Negative surgical margin and stage T2bN0M0 were confirmed. Continence was achieved immediately after cathter removal. One month after surgery, prostate specific antigen was undetectable. Erectile function was preserved 3 months postoperatively.

Conclusions:

Hem-o-lok-free and Retzius-sparing RARP is a feasible surgical approach that combines the benefits of complete retrograde release of the NVB, preserving the nerves and vascular structures around the prostate, protecting the pelvic floor structure, and ensuring rapid recovery of micturition control.
Coronavirus disease 2019 (COVID-19) and priapism: An unexplored association
Authors: Malinga Dominic Mpumelelo , Laher Abdullah E. , McDowall Jared , Adam Ahmed
Published: June 2022

Background:

Coronavirus disease 2019 (COVID-19) has an established impact on multiple organ systems, including the vascular and urogenital systems. Vascular effects may include venous thromboembolic disease, which could theoretically be a precursor to priapism—a urological emergency defined as an abnormal condition of prolonged penile erection lasting >4 hours. To better explore this association, we critically appraised all the published COVID-19 cases associated with priapism.

Materials and methods:

After PROSPERO registration (CRD42021245257), a systematic search of Google Scholar, Scopus, Embase, Web of Science, PubMed, Cumulative Index to Nursing and Allied Health Literature, Global Index Medicus, and Cochrane Database of Systematic Reviews was performed using specific search terms. The following study metadata were extracted: age, requirement for respiratory support, cavernous blood gas findings, management of priapism, and patient outcomes.

Results:

Fifteen single-patient case reports were included in this review. Of these, all of the patients presented with ischemic priapism, 9 patients (60.0%) were >60 years of age, 4 (26.7%) reported more than a single episode of priapism, 11 (73.3%) presented with pneumonia, 8 (53.3%) required mechanical ventilation, D-dimer was elevated in 5 of the 6 (83.3%) patients in whom this was reported, and among the 13 patients in whom mortality was reported, 4 (30.8%) died.

Conclusions:

Early reports suggest a prognostic relationship between COVID-19 and coexisting priapism. However, owing to commonalities in their pathophysiology and the small dataset reported in the literature, the probable association between COVID-19 and priapism is still theoretical. Further research is needed to confirm this association.
Expert Consensus on Diagnosis and Treatment of End-Stage Liver Disease Complicated with Infections
Authors: Ning Qin , Chen Tao , Wang Guiqiang , Xu Dong , Yu Yanyan , Mao Qing , Li Taisheng , Li Lanjuan , Li Jun , Lu Xiaoju , Li Jiabin , Li Zhiwei , Zhang Wenhong , Xiao Yonghong , Meng Qinghua , Mi Yuqiang , Shang Jia , Yu Yunsong , Zhao Yingren , Zhao Caiyan , Zhao Hong , Huang Jianrong , Peng Jie , Tang Hong , Tang Xiaoping , Hu Jinhua , Hu Bijie , Guo Wei , Zheng Bo , Chen Baiyi , Zhang Yuexin , Wei Jia , Sheng Jifang , Chen Zhi , Wang Minggui , Xie Qing , Wang Yuming , Wang Fu-Sheng , Hou Jinlin , Duan Zhongping , Wei Lai , Jia Jidong ,   Chinese Society of Infectious Disease of Chinese Medical Association
Published: June 2022

End-stage liver disease (ESLD) is a life-threatening clinical syndrome that markedly increases mortality in patients with infections. In patients with ESLD, infections can induce or aggravate the occurrence of liver decompensation. Consequently, infections are among the most common complications of disease progression. There is a lack of working procedure for early diagnosis and appropriate management for patients with ESLD complicated by infections as well as local and international guidelines or consensus. This consensus assembled up-to-date knowledge and experience across Chinese colleagues, providing data on principles as well as working procedures for the diagnosis and treatment of patients with ESLD complicated by infections.
Examination of Homologies between COVID-19 Vaccines and Common Allergens: The Potential for T Cell-mediated Responses for Allergic Rhinitis and Asthma
Authors: Hartwell Micah , Greiner Benjamin H. , Nicks Savannah
Published: June 2022

As the SARS-CoV-2 virus shares relatively large protein sequences homologous to grass pollens, dust mites, and molds, our objective was to assess the potential overlap between the COVID-19 mRNA vaccines from Pfizer-BioNtech and Moderna and known allergens. We found 7 common allergens with potential for cross-reactivity with the Pfizer vaccine and 19 with the Moderna vaccine, including common grasses, molds, and dust mites. T-cell mediated antigen cross-reactivity between viruses and allergens is a relatively new area of study in clinical immunology; a discipline that may be particularly useful regarding the SARS-CoV-2 virus and the allergic response in humans. These results suggest that vaccination with the Pfizer-BioNtech and Moderna COVID-19 vaccines may contribute to T-cell cross-reactivity with allergens that impact allergic asthma and allergic rhinitis. Further research should assess the clinical implications of COVID-19 vaccination on the severity and symptomatology of the allergic disease, in addition to natural viral infection.
Advances in HIV Eradication Strategies
Authors: Mei Qingmin , Wang Wei , Wu Jianjun , Gao Yong
Published: June 2022

Although the advent of combination antiretroviral therapy can efficiently suppress human immunodeficiency virus (HIV) replication, a complete cure for HIV infection cannot be achieved due to the existence of latent viral reservoirs. In recent years, investigation of HIV cure strategies has become a hot topic in the field. In this article, we review the major barriers to HIV cure, compare the progress and challenges of non-specific and specific latent reversal agents in curing HIV, and discuss possible solutions to the current problems.
MicroRNAs and their signaling pathway in mycosis fungoides
Authors: Sun Zhiyuan , Yao Xiaona , Ding Xing , Li Xun , Tian Xuewen
Published: June 2022

Background:

Oncogenic microRNAs, a kind of stable epigenetic inhibitors, often deregulated in Mycosis fungoides (MF) which affect the skin and tend to transform and spread.

Results:

Previous studies investigating the de-expression of microRNA in MF patients skin biopsies identified that they were not only regulated by signaling pathway, but also regulated other signaling pathway. Furthermore, studies have elucidated the molecular mechanisms of the STAT signaling pathway that can promote a great diversity of miRNA expression via cytokine binding receptors, activating Janus kinase-3 and STAT proteins. But some non-STAT signaling pathway with mircoRNA de-expression in MF was incomplete.

Conclusion:

Taken together, these studies demonstrate that microRNA may be used as the prognosis, progression and diagnose of MF, as they can not only control MF cell proliferation, but also induce MF cell apoptosis.
Analyzing adverse drug reaction using statistical and machine learning methods
Authors: Kim Hae Reong , Sung MinDong , Park Ji Ae , Jeong Kyeongseob , Kim Ho Heon , Lee Suehyun , Park Yu Rang
Published: June 2022

Background:

Adverse drug reactions (ADRs) are unintended negative drug-induced responses. Determining the association between drugs and ADRs is crucial, and several methods have been proposed to demonstrate this association. This systematic review aimed to examine the analytical tools by considering original articles that utilized statistical and machine learning methods for detecting ADRs.

Methods:

A systematic literature review was conducted based on articles published between 2015 and 2020. The keywords used were statistical, machine learning, and deep learning methods for detecting ADR signals. The study was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement (PRISMA) guidelines.

Results:

We reviewed 72 articles, of which 51 and 21 addressed statistical and machine learning methods, respectively. Electronic medical record (EMR) data were exclusively analyzed using the regression method. For FDA Adverse Event Reporting System (FAERS) data, components of the disproportionality method were preferable. DrugBank was the most used database for machine learning. Other methods accounted for the highest and supervised methods accounted for the second highest.

Conclusions:

Using the 72 main articles, this review provides guidelines on which databases are frequently utilized and which analysis methods can be connected. For statistical analysis, >90% of the cases were analyzed by disproportionate or regression analysis with each spontaneous reporting system (SRS) data or electronic medical record (EMR) data; for machine learning research, however, there was a strong tendency to analyze various data combinations. Only half of the DrugBank database was occupied, and the k-nearest neighbor method accounted for the greatest proportion.
Proposal of a novel protocol using estimated cardiac index fractional dose to improve aortic contrast enhancement for early-phase dynamic CT
Authors: Kuba Tadashi , Tokushige Akihiro , Murayama Sadayuki , Ueda Shinichiro
Published: June 2022

Maximum aortic computed tomography value (CTV) is difficult to control because of variations in cardiac function and patient physique. Therefore, to improve early-phase aortic enhancement on dynamic computed tomography (CT), we developed an estimated cardiac index fractional dose (eciFD). The eciFD protocol is a novel and original protocol for administering fractional dose (FD), representing the amount of iodine per unit body weight per injection duration, based on cardiac index (cardiac output divided by body surface area) as estimated by age in early-phase dynamic CT. At the time of administration, by selecting FD based on the patient's age and selecting a parameter that can achieve this FD, an aortic CTV ≥300 HU (ACTV≥300) can be obtained. This study aimed to investigate aortic enhancement on CT angiography using the eciFD protocol.

This retrospective study investigated 291 consecutive patients who underwent dynamic CT from neck to abdomen after recommendation of the eciFD protocol at our institution. We compared early-phase aortic CTV distributions by scan delay between an eciFD group (eciFD applied, n = 135) and a non-eciFD group (eciFD not applied, n = 80). The effect of eciFD on early-phase ACTV≥300 was evaluated using logistic regression analysis adjusted for several potentially meaningful clinical confounders related to aortic CTV, namely male sex, heart rate ≤80 beats/min, estimated glomerular filtration rate ≤40 mL/min, use of eciFD, bolus tracking (BT), history of myocardial infarction, and order from the emergency center.

The eciFD protocol was a significant factor for early-phase ACTV≥300 after adjusting for several confounders (odds ratio 3.03; 95% confidence intervals 1.59–5.77; P = .001). No interaction was seen between BT and eciFD protocol (p for interaction = 0.76). In terms of CTV distribution, with both a fixed scan delay time and BT, the eciFD group showed a high aortic CTV. The combination of eciFD protocol with BT provided a particularly high percentage of patients with ACTV≥300 (86.4%).

The eciFD protocol was useful for improving aortic contrast enhancement. These findings need to be validated in a randomized controlled study.
Contribution of interleukin 27 serum level to pathogenesis and prognosis in children with immune thrombocytopenia
Authors: Hassan Tamer , Abdel Rahman Doaa , Raafat Nermin , Fathy Manar , Shehab Mohamed , Hosny Ahmed , Fawzy Reham , Zakaria Marwa
Published: June 2022

Concepts surrounding the mechanisms of thrombocytopenia in ITP have shifted from the traditional view of autoantibody mediated platelet destruction to more complex mechanisms in which impaired platelet production, T-cell-mediated effects, and disturbed cytokine profiles play a role. Interleukin 27 (IL-27) plays pleiotropic roles in immunomodulation and autoimmune diseases.

We aimed to determine the level of IL-27 in patients with ITP and its relationship to patient and disease characteristics as well as disease chronicity and response to treatment.

Sixty childrens with primary immune thrombocytopenia were consequetively enrolled in this study as well as 20 age and sex matched healthy controls.

ITP patients had significantly higher levels of IL-27 than controls (770.6 and 373.8 pg/ml, respectively). Patients with acute ITP had the highest levels of IL-27 among patient groups, while patients in remission had the lowest IL-27 levels (860.1and 622.9 pg/ml, respectively). Patients who received IVIG and combined steroids plus IVIG had significantly higher IL-27 levels than others. Patients who received Eltrombopag had significantly lower IL-27 levels than others.

IL-27 seems to play a role in pathogenesis of childhood ITP. IL-27 can be used as a predictor for disease occurrence as well as responsiveness to treatment.
Initial preclinical evaluation of 68Ga-DOTA-(Ser)3-LTVSPWY peptide as a PET radiotracer for glioblastoma targeting and imaging
Authors: Ranjbar Venousheh , Molavipordanjani Sajjad , Biabani Ardakani Javad , Akhlaghi Mehdi , Nikkholgh Babak , Hosseinimehr Seyed Jalal
Published: June 2022

Purpose

Imaging of glioblastoma multiform (GBM) tumor using 68-Galium-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraaceticacid-Ser-Ser-Ser-Leu-Thr-Val-Ser-Pro-Trp-Tyr (68Ga-DOTA-(Ser)3-LTVSPWY) as a PET radiotracer for HER2 receptor due to fact that this receptor plays a pivotal role in the tumorigenesis and tumor progression in a wide range of cancer.

Methods

68Ga-DOTA-(Ser)3-LTVSPWY was produced with high radiochemical purity. The affinity and specificity of this radiotracer toward HER2 receptor on the surface of glioma glioblastoma (U-87 MG) cell line were evaluated. Furthermore, the biodistribution and PET imaging of this radiolabeled peptide were investigated on xenografted U-87 MG tumor-bearing mice.

Results

The in-vitro specific binding study revealed that the 68Ga-DOTA-(Ser)3-LTVSPWY binds to different cell lines with respect to their level of HER2 expression. The calculated KD and Bmax of radiolabeled peptide toward U-87 MG cell line were 5.5 ± 2.4 nmol/l and (2.4 ± 0.3) × 105 receptors per cell, respectively. The highest tumor uptake was observed at 30-min postinjection, whereas the tumor-to-muscle ratio was about four-fold. The acquired PET images distinctively show tumor site, which was blocked with excess nonlabeled peptide that revealed specific in-vivo targeting of 68Ga-DOTA-(Ser)3-LTVSPWY for glioma.

Conclusion

68Ga-DOTA-(Ser)3-LTVSPWY specifically recognizes HER2 receptors and could be a potential candidate for GBM imaging.
Use of Tranexamic Acid in Liposculpture: A Double-Blind, Multicenter, Randomized Clinical Trial.
Authors: Hoyos Alfredo E. , Duran Héctor , Cardenas-Camarena Lazaro , Bayter Jorge E. , Cala Laura , Perez Mauricio , Lopez Alejandro , Talleri Giancarlo , Domínguez-Millan Rodrigo , Mogollon Ivan R.
Published: June 2022

BACKGROUND:

Intraoperative hemostasis should be performed with great caution since bleeding is a huge enemy of patient safety during surgery. Tranexamic acid (TXA) is a lysine synthetic derivate that inhibits fibrinolysis and diminishes the bleeding by blocking the 5 lysine-binding sites for plasminogen.

PURPOSE:

We are comparing the efficacy of tranexamic acid vs. placebo as a hemostatic agent in liposculpture procedures.

METHODS Design, Setting and Participants:

We conducted a multicenter, double-blinded, randomized, controlled clinical trial in patients who were scheduled for liposculpture in 3 plastic surgery centers (Colombia and Mexico) between January 2019 and February of 2020. Interventions: 141 patients were randomly assigned into three groups: Intravenous (1 gr of TXA), subcutaneous (1 gr of TXA) and placebo (Normal Saline). 47 patients were assigned to each group. 30 patients were male and 111 were female. Main outcome: Evaluate the amount of postoperative bleeding between groups. The primary outcome was measured by the hemoglobin (Hb) point loss at day 1 (Preoperative Hb minus Hb at day 1 postop) and the Hb (mg/dl) point loss at day 5 (Preoperative Hb minus Hb at day 5 postop).

RESULTS:

We found the Intravenous intervention group to have a greater hemoglobin level than the other two groups on both the first postoperative day (P=0.0001) and the fifth postoperative day (P=0.001). There were no statistical differences in Hb values between the placebo and the subcutaneous intervention groups.

CONCLUSIONS:

Intravenous Tranexamic acid is a good therapeutic choice to implement on liposculpture procedures to decrease postoperative bleeding.
Vertical “V-Y” Advancement Lifting Based on Fat Compartments: A New Approach for Lower Eyelid and Midcheek Rejuvenation
Authors: Sun Xiaoming , Chen Xiangling , Zhang Lu , Zhang Ying , Jin Rong , Mao Xiyuan , Cheng Liying , Bian Weiwei , Zhang Yuguang
Published: June 2022

Background:

Lower blepharoplasty continues to improve over time. With discovery of the numerous fat compartments of the face, surgeons noticed that the appearance of the lower eyelid area through aging could be improved through midface lifting. This study introduces a vertical “V-Y” advancement lifting technique, using the concept of fat compartments for lower lid and midcheek rejuvenation.

Methods:

Eighty female patients were categorized into four age groups at 20 patients each from 20- to 59-year-olds. The average measurement for the lower lid length in each group was recorded. Additionally, 318 patients underwent lower eyelid blepharoplasty combined with fat compartments advancement lifting for lid-cheek area rejuvenation from April 2015 to May 2018 were included in this study. The postoperative effect was evaluated based on pre- and postoperative photographs, lower lid length measurements, and three-dimensional facial analyses.

Results:

The lower lid lengths gradually increased with age, and the greatest increase occurred in the 30- to 39-year-old group. 318 Asian female patients underwent the surgical procedure, with the patients’ age ranging from 35 to 58 years old. Measurements of the lower lid length showed an average reduction of 0.31cm 6 months post-surgery. Three-dimensional facial analysis also indicated that the patient's midcheek volume increased at varying degrees post-surgery.

Conclusions:

Lower eyelid blepharoplasty combined with vertical “V-Y” advancement lifting makes it possible to restore facial fat compartments. This procedure improves projection in the midcheek without any kinds of fillers, thus achieving a more youthful appearance of the lower lid and lid-cheek contour in middle-aged women.
Lack of Workplace Support for Obstetric Health Concerns is Associated With Major Pregnancy Complications
Authors: Rangel Erika L. , Castillo-Angeles Manuel , Hu Yue-Yung , Gosain Ankush , Easter Sarah Rae , Cooper Zara , Atkinson Rachel B. , Kim Eugene S.
Published: June 2022

Objective:

We sought to assess whether lack of workplace support for clinical work reductions during pregnancy was associated with major pregnancy complications.

Background:

Surgeons are at high risk of major pregnancy complications. Although rigorous operative schedules pose increased risk, few reduce their clinical duties during pregnancy.

Methods:

An electronic survey was distributed to US surgeons who had at least 1 live birth. Lack of workplace support was defined as: (1) desiring but feeling unable to reduce clinical duties during pregnancy due to failure of the workplace/training program to accommodate and/or concerns about financial penalties, burden on colleagues, requirement to make up missed call, being perceived as weak; (2) disagreeing colleagues and/or leadership were supportive of obstetrician-prescribed bedrest. Multivariate logistic regression determined the association between lack of workplace support and major pregnancy complications.

Results:

Of 671 surgeons, 437 (65.13%) reported lack of workplace support during pregnancy and 302 (45.01%) experienced major pregnancy complications. Surgeons without workplace support were at higher risk of major pregnancy complications than those who had workplace support (odds ratio: 2.44; 95% confidence interval: 1.58–3.75). Bedrest was prescribed to 110/671 (16.39%) surgeons, 38 (34.55%) of whom disagreed that colleagues and/or leadership were supportive. Of the remaining surgeons, 417/560 (74.5%) desired work reductions but were deterred by lack of workplace support.

Conclusions:

Lack of workplace support for reduction in clinical duties is associated with adverse obstetric outcomes for surgeons. This is a modifiable workplace obstacle that deters surgeons from acting to optimize their infant’s and their own health. To ensure the health of expectant surgeons, departmental policies should support reduction of clinical workload in an equitable manner without creating financial penalties, requiring payback for missed call duties, or overburdening colleagues.
Carotid Intervention Improves Cognitive Function in Patients With Severe Atherosclerotic Carotid Disease
Authors: Zhou Wei , Succar Bahaa , Murphy Devin P. , Ashouri Yazan , Chou Ying-Hui , Hsu Chiu-Hsieh , Rapcsak Steven , Trouard Theodore
Published: June 2022

Introduction:

Carotid revascularization procedures are effective in stroke prevention in appropriately selected patients. We sought to understand the effects of the carotid intervention on cognitive function in a well-defined cohort of prospectively recruited patients.

Methods:

A total of 170 consecutive patients undergoing carotid intervention for severe carotid stenosis were recruited. Patients received neuropsychometric testing preintervention, and at 1, 6, and 12 months postoperative. Patients were screened with the Mini-Mental State Examination. Rey Auditory Verbal Learning test (RAVLT) test was the primary outcome measure and multiple cognitive tests were used to evaluate executive function. Paired t test and McNemar test were performed to compare age-adjusted and education-adjusted postoperative scores at the individual time point with the preoperative scores.

Results:

Our patients had a high prevalence of cardiovascular risks and 51.2% of whom were symptomatic. The usages of statin and antiplatelet were high (88.8% and 69.4%, respectively). A total of 140 patients had 1 or more postoperative neuropsychometric tests in addition to their preoperative tests were included. The average RAVLT preoperative score was lower (z=−0.79, SD=1.3, confidence interval: −1 to −0.53) than the age-adjusted norm. We observed a significant improvement in RAVLT memory scores at 1 and 6 months postoperative compared with preoperative. We also observed significant improvement in multiple executive functions measures up to 12 months postoperative. The improvement on patients with preoperative stroke symptoms was less consistent.

Conclusions:

This prospective study showed that carotid intervention improved memory and executive function in patients with the severe carotid occlusive disease. It highlights the cognitive benefit of the carotid intervention in appropriately selected patients.
Intrathecal Morphine and Effect on Opioid Consumption and Functional Recovery after Pancreaticoduodenectomy
Authors: Burchard Paul R , Melucci Alexa D , Lynch Olivia , Loria Anthony , Dave Yatee A , Strawderman Myla , Schoeniger Luke O , Galka Eva , Moalem Jacob , Linehan David C
Published: June 2022

BACKGROUND:

Single-shot intrathecal morphine (ITM) is an effective strategy for postoperative analgesia, but there are limited data on its safety, efficacy, and relationship with functional recovery among patients undergoing pancreaticoduodenectomy.

STUDY DESIGN:

This was a retrospective review of patients undergoing pancreaticoduodenectomy from 2014 to 2020 as identified by the institutional NSQIP Hepato-pancreato-biliary database. Patients were categorized by having received no spinal analgesia, ITM, or ITM with transversus abdominus plane block (ITM+TAP). The primary outcomes were average daily pain scores from postoperative days (POD) 0 to 3, total morphine equivalents (MEQ) consumed over POD 0 to 3, and average daily inpatient MEQ from POD 4 to discharge. Secondary outcomes included the incidence of opioid related complications, length of stay, and functional recovery.

RESULTS:

A total of 233 patients with a median age of 67 years were included. Of these, 36.5% received no spinal analgesia, 49.3% received ITM, and 14.2% received ITM+TAP. Average pain scores in POD 0 to 3 were similar by mode of spinal analgesia (none [2.8], ITM [2.6], ITM+TAP [2.3]). Total MEQ consumed from POD 0 to 3 were lower for patients who received ITM (121 mg) and ITM+TAP (132 mg), compared with no spinal analgesia (232 mg) (p < 0.0001). Average daily MEQ consumption from POD 4 to discharge was lower for ITM (18 mg) and ITM+TAP (13.1 mg) cohorts compared with no spinal analgesia (32.9 mg) (p = 0.0016). Days to functional recovery and length of stay were significantly reduced for ITM and ITM+TAP compared with no spinal analgesia. These findings remained consistent through multivariate analysis, and there were no differences in opioid-related complications among cohorts.

CONCLUSIONS:

ITM was associated with reduced early postoperative and total inpatient opioid utilization, days to functional recovery, and length of stay among patients undergoing pancreaticoduodenectomy. ITM is a safe and effective form of perioperative analgesia that may benefit patients undergoing pancreaticoduodenectomy.
Spatiotemporally selective ATP events from astrocytes encode injury information and guide sustained microglial response
Authors: Chen Yue , Luan Pengwei , Liu Juan , Wei Yelan , Wu Zhaofa , Jing Miao
Published: June 2022

Brain injuries, either directly result from external assaults or are accompanied with diseases, initiate a cascade of intrinsic responses for damage management, with resident microglia as one of the key responders in the early phase of reaction. Changes in microglia including their motility and activities can be tuned according to injury intensity and position, indicating such injury information is precisely encoded and actively presented. Also, microglia in a broad area can perform sustained migration towards a transient and local injury, suggesting a signal amplification process may exist that bridge differences between injury and microglial migration in time and space. Currently, the molecular identity and underlying mechanism for injury encoding, amplification and presentation have not been fully elucidated yet, although candidate molecules like ATP are linked with both injury and microglial response. Based upon our recent technique advancement in engineering novel genetically-encoded ATP sensors, we here identified and characterized that in the cortex of awake mice in vivo, a new type of spatiotemporally selective ATP events, referred to as Inflares, was selectively evoked after brain injuries, which were actively and repeatedly generated from astrocytes in a Ca2+-dependent manner through the opening of pannexin 1 channel. Functionally, Inflares amplified local injury over time and space with their persistence and widespread distribution, and provided continuous directionality that was necessary for guiding microglial migration. Excessive Inflares in pathological injuries drove microglial dysfunction and caused secondary damage, whereas blocking Inflares successfully reversed pathological changes and benefited the outcome of ischemic stroke. Together, we identified the internal mechanism that encoded and presented injury information, and provided rational target for treating injury-related diseases.
Spatial regulation of Drosophila ovarian Follicle Stem Cell division rates and cell cycle transitions
Authors: Melamed David , Choi Aaron , Reilein Amy , Kalderon Daniel
Published: June 2022

Drosophila ovarian Follicle Stem Cells (FSCs) present a favorable paradigm for understanding how stem cell division and differentiation are balanced in communities where they can be regulated independently. Many key extracellular signals for FSCs have been identified, including inversely graded Wnt and JAK-STAT pathway activators. FSCs also exhibit interesting functional spatial heterogeneity; posterior FSCs become proliferative Follicle Cells, while anterior FSCs become quiescent Escort Cells at a much lower rate. Here, by using live imaging and FUCCI cell-cycle reporters, we measured absolute division rates and found that posterior FSCs cycle 3-4 times faster than their anterior neighbors, matching their increased differentiation rate. We also found evidence for FSC G2/M cycling restrictions and G1/S restriction that increases more anteriorly, especially beyond the FSC domain. JAK-STAT signaling promotes both transitions but graded JAK-STAT signaling alone does not explain the graded cycling of FSCs. Genetic interaction tests and FUCCI reporter assays suggest that JAK-STAT signaling acts partly through Yorkie and can largely substitute for stimulation of division by Hh signaling. PI3 kinase signaling, in contrast to Hh signaling, acts largely independently of Yorkie induction and stimulates the G2/M transition.
Native holdup (nHU) to measure binding affinities from cell extracts
Authors: Zambo Boglarka , Morlet Bastien , Negroni Luc , Trave Gilles , Gogl Gergo
Published: June 2022

Characterizing macromolecular interactions is essential for understanding cellular processes, yet nearly all methods used to detect protein interactions from cells are qualitative. Here, we introduce the native holdup (nHU) approach to quantify equilibrium binding constants and explore binding mechanisms of protein interactions from cell extracts. Compared to other pulldown-based assays, nHU requires less sample preparation and can be coupled to any analytical methods, such as western blotting (nHU-WB) or mass spectrometry (nHU-MS) as readouts. We use nHU to explore interactions of SNX27, a cargo adaptor of the retromer complex and find good agreement between in vitro affinities and those measured directly from cell extracts using nHU. This challenges the unwritten paradigm stating that biophysical parameters like binding constants cannot be accurately determined from cells or cellular extracts. We discuss the strengths and limitations of nHU and provide simple protocols that can be implemented in most laboratories.
A unified peptide array platform for antibody epitope binning, mapping, specificity and predictive off-target binding
Authors: Moore Cody , Lei Anna , Walsh Patrick , Trenchevska Olgica , Saini Gaurav , Tarasow Theodore M. , Srinivasan Mohan , Smith David , Greving Matthew P.
Published: June 2022

Therapeutic antibody efficacy is largely determined by the target epitope. In addition, off-target binding can result in unanticipated side-effects. Therefore, characterization of the epitope and binding specificity are critical in antibody discovery. Epitope binning provides low-resolution of an antibody epitope and is typically performed as a cross-blocking assay to group antibodies into overlapping or non-overlapping bins. Epitope mapping identifies the epitope with high resolution but requires low throughput methods. In addition to binning and mapping, there is a need for a scalable and predictive approach to reveal off-target binding early in antibody discovery to reduce the risk of in vivo side effects. Peptide microarrays are an information-rich platform for antibody characterization. However, the potential of peptide microarrays in early-stage antibody discovery has not been realized because they are not produced at the scale, quality and format needed for reliable high-throughput antibody characterization. A unified, peptide library platform for high-resolution antibody epitope binning, mapping and predictive off-target binding characterization is described here. This platform uses highly scalable array synthesis and photolithography to synthesize more than 3 million addressable peptides. These arrays conform to a microplate format and each synthesis is qualified with mass spectrometry. Using this platform, a scalable approach to early-stage epitope and specificity characterization, with prediction of off-target interaction(s), is demonstrated using a panel of anti-HER2 monoclonal antibodies. This study highlights the prospect of this platform to improve antibody discovery productivity by generating epitope and specificity information much earlier with potentially hundreds of antibody clones.
Explicitly Nonlinear Dynamic Functional Network Connectivity In Resting-State fMRI Data
Authors: Motlaghian S. M. , Belger A. , Bustillo J. R. , Faghiri A. , Ford J. M. , Iraji A. , Lim K. , Mathalon D. H. , Miller R. , Mueller B. A. , O’Leary D. , Pearlson G. , Potkin S. G. , Preda A. , van Erp T.G. , Calhoun V. D.
Published: June 2022

Most dynamic functional connectivity in fMRI data is focused on linear correlations, and to our knowledge, no study has studied whole brain explicitly nonlinear dynamic relationships within the data. While some approaches have attempted to study overall connectivity more generally using flexible models, we are particularly interested in whether the non-linear relationships, above and beyond linear, are capturing unique information. This study thus proposes an approach to assess the explicitly nonlinear dynamic functional network connectivity derived from the relationship among independent component analysis time courses. Linear relationships were removed at each time point to evaluate, typically ignored, explicitly nonlinear dFNC using normalized mutual information. Simulations showed the proposed method accurately estimated NMI over time, even within relatively short windows of data. Results on fMRI data included 151 schizophrenia patients, and 163 healthy controls showed three unique, highly structured, mostly long-range, functional states that also showed significant group differences. This analysis identifies a higher level of explicitly nonlinear dependencies in transient connectivity within the visual network in healthy controls compared to schizophrenia patients. In particular, nonlinear relationships tend to be more widespread than linear ones. We also find highly significant differences in the relative co-occurrence of linear and explicitly nonlinear states in HC and SZ, suggesting these may be an important aspect of the disorder. Overall, this work suggests that quantifying nonlinear dependencies of dynamic functional connectivity may provide a complementary and potentially valuable tool for studying brain function by exposing relevant variation that is typically ignored.
Acacia sieberiana (Fabaceae) Attenuates Paracetamol and Bile Duct Ligation-Induced Hepatotoxicity via Modulation of Biochemical and Oxidative Stress Biomarkers
Authors: Watafua Miriam , Ejiofor Jane I. , Musa Aminu , Ahmad Mubarak Hussaini
Published: June 2022

Background

The plant Acacia sieberiana (Fabaceae) is traditionally used to manage hepatitis. This research work aims to investigate the hepatoprotective effectiveness of root bark extract of Acacia sieberiana (ASE) against paracetamol (PCM) and bile duct ligation (BDL)-induced hepatotoxicity. The phytochemical and median lethal dose (LD50) investigations were conducted. The rats were pre-treated with the ASE (250, 750, 1,500 mg/kg) once daily via oral route for 7 consecutive days. On the 8th day, liver injury was initiated by PCM administration (2g/kg). Similarly, in the BDL-induced liver injury, the animals were administered ASE (125, 250 and 380 mg/kg) intraperitoneally for 7 consecutive days. After 24 hours, blood samples and hepatic tissues were obtained for biochemical and histopathological investigations.

Results

Phytocomponents determination revealed glycosides, triterpenes, glycosides, saponins, tannins, flavonoids and alkaloids. The oral and intraperitoneal LD50 values of the ASE were >5,000 and 1,300 mg/kg, respectively. The ASE efficiently (p<0.05) decreased the alanine transaminase (ALT) and aspartate transaminase (AST) levels and elevated the albumin and total protein (TP) levels. The direct bilirubin effectively (p<0.05) decreased at 750 mg/kg. Besides, the extract efficiently elevated the glutathione peroxidase (GPx), superoxide dismutase (SOD), and catalase (CAT) in relation to the PCM hepatotoxic group. Also, the malondialdehyde (MDA) concentration was reduced by the ASE. Meanwhile, in the BDL– induced liver injury, the ASE remarkably (p<0.05) declined the AST, ALP, bilirubin and MDA. Besides, there was effective (p<0.05) elevation in SOD, GPx and CAT in the ASE-treated groups. The morphology of liver tissue was preserved at 125 and 250 mg/kg ASE groups from BDL-induced necrosis and vascular congestion.

Conclusion

The study shows that the ASE has hepatoprotective actions against liver damage by possible modulation of biochemical and oxidative stress biomarkers