bluuebunny/crossref_metadata_2025 huggingface dataset:
Treatment options for endometrial hypoproliferation
Authors: Cakiroglu Yigit , Tiras Bulent , Franasiak Jason , Seli Emre
Published: March 2023

Purpose of review

Endometrial hypoproliferation refers to the failure of the endometrium to reach optimal thickness during fresh or frozen embryo transfer cycles in women undergoing infertility treatment with in-vitro fertilization (IVF). This review discusses the treatment options for endometrial hypoproliferation.

Recent findings

Apart from factors related to the embryo quality, ultrasonographic findings associated with the endometrium, such as endometrial thickness, endometrial pattern and subendometrial blood flow, are considered key factors associated with the outcome of assisted reproductive treatment. To date, a consensus has not been reached regarding the definition of thin endometrium, while thresholds of 6, 7 or 8 mm have been used in the literature. Strategies to increase endometrial thickness can be reviewed in three groups: endocrine approaches, vitamins & supplements, and new experimental therapeutic interventions. Some of the recently introduced experimental therapeutic interventions such as platelet-rich plasma injection, stem cell treatment and tissue bioengineering are exciting potential therapies that need to be further studied.

Despite a large number of publications on the topic, diagnosing and treating endometrial hypoproliferation remains a challenge. Well designed studies are needed to establish a widely accepted endometrial thickness cut-off value below which endometrial hypoproliferation is diagnosed and to generate meaningful data that would allow an evidence-based discussion of available therapeutic options with patients.
Double stimulation for the management of poor-prognosis patients: where are we going?
Authors: Petrone Pasquale , Vaiarelli Alberto , Blockeel Christophe
Published: March 2023

Purpose of review

The technical improvements in IVF allowed the implementation of nonconventional ovarian stimulation protocols for some specific patients. Where time is crucial, such as with oncologic patients, poor-prognosis patients, patients with low ovarian reserve, and those with advanced maternal age, access to IVF treatment is even more critical. Some of these protocols might start in the late follicular phase, luteal phase, or involve both stimulations within the same ovarian cycle.

Recent findings

Until now, published evidence showed that oocytes retrieved from unconventional protocol seem to be developmentally, genetically, and reproductively competent. Second stimulation in the same ovarian cycle after the conventional approach may represent a sound alternative to oocyte accumulation. This can be proposed in progress after careful counselling focused on the patients’ chances of finding at least one euploid embryo on account of their age and of the number of blastocysts obtained after the conventional approach.

The adoption of these new strategies, known as double stimulation protocol, can be conceived as a real full-personalization of ovarian stimulation. Multicentre prospective RCTs are urgently needed to evaluate the efficacy, efficiency, and costs of double stimulation versus two consecutive conventional approaches with standard or mild stimulation and in a different IVF setting.
The Utility of a Lateral Adipodermal Flap in Prepectoral Direct-to-implant Breast Reconstruction
Authors: Schwartz Jean-Claude D.
Published: March 2023

Prepectoral implant-based breast reconstruction has become more common given the reduced dissection, decreased postoperative pain, elimination of animation deformity, and improved aesthetics compared with subpectoral reconstructions. Despite these benefits, surgeons must contend with increased rates of implant rippling and more tenuous implant positioning and coverage, especially in direct-to-implant reconstructions. Although the use of an acellular dermal matrix can assist with both implant rippling and support/positioning, it does not protect against implant exposure, and rippling can still occur, despite its use, with significant additional cost. This article looks into the use of a lateral adipodermal flap that assists with reducing the mismatch between the excess skin and implant surface area, implant positioning (by helping secure the lateral mammary fold), and providing implant coverage. Twenty-two patients underwent 38 nipple-sparing mastectomies and prepectoral direct-to-implant reconstructions using a lateral adipodermal flap without acellular dermal matrix. No patients had evidence of implant malposition or exposure with at least 6 months follow-up. The author concludes that the lateral adipodermal flap may be helpful in securing the lateral mammary fold, reducing excess skin and providing viable tissue coverage in patients undergoing prepectoral direct-to-implant reconstruction.
Management of Severe Extended Burn Axillary Contracture in a Low-resource Setting
Authors: Jean-Louis Willy F. , Mixter Roger C. , Jean-Louis McLee , Duffy Frederick
Published: March 2023

Contracture is a common complication of deep burn injury, affecting up to one-third of patients. Although some degree of contracture occurs in any setting, severe extended axillary contractures are more often due to unavailable or inappropriate care. Very few cases have been described in the literature. Their management can be especially challenging in a low-resource environment. The purpose of this article is to present two cases in which severe postburn axillary contractures were effectively managed in a low resource setting, using an island perforator flap coupled with a skin graft or advancement flap. In severe extended axillary contracture, more than one technique is often required to cover the large defect created after contracture release.
A Comprehensive Secondary Prevention Benchmark (2PBM) Score Identifying Differences in Secondary Prevention Care in Patients After Acute Coronary Syndrome
Authors: Haegele Matthias , Liu Yu-Ching , Frey Simon , Strebel Ivo , Jordan Fabian , Wick Rupprecht , Burkard Thilo , Clerc Olivier Florian , Pfister Otmar
Published: March 2023

Purpose:

The objective of this study was to quantify secondary prevention care by creating a secondary prevention benchmark (2PBM) score for patients undergoing ambulatory cardiac rehabilitation (CR) after acute coronary syndrome (ACS).

Methods:

In this observational cohort study, 472 consecutive ACS patients who completed the ambulatory CR program between 2017 and 2019 were included. Benchmarks for secondary prevention medication and clinical and lifestyle targets were predefined and combined in the comprehensive 2PBM score with maximum 10 points. The association of patient characteristics and achievement rates of components and the 2PBM were assessed using multivariable logistic regression analysis.

Results:

Patients were on average 62 ± 11 yr of age and predominantly male (n = 406; 86%). The types of ACS were ST-elevation myocardial infarction (STEMI) in 241 patients (51%) and non–ST-elevation myocardial infarction in 216 patients (46%). Achievement rates for components of the 2PBM were 71% for medication, 35% for clinical benchmark, and 61% for lifestyle benchmark. Achievement of medication benchmark was associated with younger age (OR = 0.979: 95% CI, 0.959-0.996, P = .021), STEMI (OR = 2.05: 95% CI, 1.35-3.12, P = .001), and clinical benchmark (OR = 1.80: 95% CI, 1.15-2.88, P = .011). Overall ≥8 of 10 points were reached by 77% and complete 2PBM by 16%, which was independently associated with STEMI (OR = 1.79: 95% CI, 1.06-3.08, P = .032).

Conclusions:

Benchmarking with 2PBM identifies gaps and achievements in secondary prevention care. ST-elevation myocardial infarction was associated with the highest 2PBM scores, suggesting best secondary prevention care in patients after ST-elevation myocardial infarction.
In Silico and In Vitro Approach for Validating the Inhibition of Matrix Metalloproteinase-9 by Quercetin
Authors: Huynh Cassandra Bonnie , Nagaarudkumaran Nijani , Kalyaanamoorthy Subha , Ngo William
Published: March 2023

Purpose:

To validate the mechanism and inhibitory activity of quercetin against matrix metalloproteinase-9 (MMP-9) using a hybrid in silico and in vitro approach.

Methods:

The structure of MMP-9 was obtained from the Protein Data Bank, and the active site was identified using previous annotations from the Universal Protein Resource. The structure of quercetin was obtained from ZINC15. Molecular docking was performed to quantify the binding affinity of quercetin to the active site of MMP-9. The inhibitory effect of various concentrations of quercetin (0.0025, 0.025, 0.25, 1.0, and 1.5 mM) on MMP-9 was quantified using a commercially available fluorometric assay. The cytotoxicity of quercetin to immortalized human corneal epithelial cells (HCECs) was quantified by obtaining the metabolic activities of the cells exposed to various concentrations of quercetin for 24 hr.

Results:

Quercetin interacts with MMP-9 by binding within the active site pocket and interacting with residues LEU 188, ALA 189, GLU 227, and MET 247. The binding affinity predicted by molecular docking was −9.9 kcal/mol. All concentrations of quercetin demonstrated significant inhibition of MMP-9 enzyme activity (all P<0.03). There was little to no reduction of HCEC metabolic activity after a 24-hr exposure to all concentrations of quercetin (P>0.99).

Conclusions:

Quercetin inhibited MMP-9 in a dose-dependent manner and was well-tolerated by HCECs, suggesting a potential role in therapy for diseases with upregulated MMP-9 as part of its pathogenesis.
Comparison of stone-free rate between percutaneous nephrolithotomy and retrograde intrarenal surgery
Authors: Chen Peng , Wei Tony Tzu-Chun , Huang Eric Yi-Hsiu , Lin Tzu-Ping , Huang Tzu-Hao , Lin Chih-Chieh , Huang I-Shen , Huang William J.
Published: March 2023

Background:

The management of urolithiasis in the kidney has been drastically changed in the era of endourology, mainly consisting of three surgical procedures: extracorporeal shock wave lithotripsy (ESWL), percutaneous nephrolithotomy (PCNL), and retrograde intrarenal surgery (RIRS). Since ESWL is usually less invasive via ambulatory clinic routes, this study aimed to examine the stone-free rate (SFR) between PCNL and RIRS.

Methods:

We retrospectively reviewed patients who had renal stones and were treated with either PCNL or RIRS from June 2016 to June 2018. Staghorn stones, stones with diameters <1 cm, and stones with diameters >2 cm were excluded. Patients who underwent multiple surgeries for bilateral renal stones and those with graft kidney stones were excluded from the study. X-ray, sonography, and/or computed tomography (CT) were used to calculate the size of the stones. Follow-up was evaluated by the same image examination within three months after surgery. Stone-free was defined as no residual stone or the presence of asymptomatic calculi <4 mm. The operation time was defined as a skin-to-skin interval.

Results:

Following exclusion criteria, there were 39 patients in each arm, with no difference in age, sex, or any other demographic data. The average stone size in the PCNL and RIRS groups was 16.3 and 14.0 mm, respectively (p = 0.009). There was no significant difference in SFR (71.8% vs 61.5%, p = 0.337); the operation time was significant longer (p < 0.001), and the hospital stay was significantly shorter (p < 0.001) in the RIRS group.

Conclusion:

PCNL and RIRS are both feasible options for managing kidney stones. However, the initial stone size might affect the selection of operation. The SFR in the PCNL group was numerically but not statistically higher. The RIRS group, on the other hand, had a longer operation time but a shorter hospital stays.
The correlation of intraoperative oliguria with acute kidney injury after noncardiac surgery: a systematic review and meta-analysis
Authors: Pang Zhaohua , Liang Shuang , Xing Manyu , Zhou Nannan , Guo Qulian , Zou Wangyuan
Published: March 2023

Background:

Acute kidney injury (AKI) occurs commonly after major surgery and is correlated with increased in-hospital morbidity and mortality. There is no consensus on whether intraoperative oliguria affects postoperative AKI. We conducted a meta-analysis to systematically assess the correlation of intraoperative oliguria with postoperative AKI.

Methods:

PubMed, Embase, Web of Science, and Cochrane Library databases were searched to identify reports on the relationship between intraoperative oliguria and postoperative AKI. Quality was assessed using the Newcastle–Ottawa Scale. The primary outcomes were the unadjusted and multivariate-adjusted odds ratios (ORs) for intraoperative oliguria to correlate with postoperative AKI. The secondary outcomes included intraoperative urine output in the AKI and non-AKI groups, the demand for postoperative renal replacement therapy (RRT), in-hospital mortality, and length of hospital stay in the oliguria and non-oliguria groups.

Results:

Nine eligible studies with 18 473 patients were included. The meta-analysis revealed that patients with intraoperative oliguria had a considerably greater risk of postoperative AKI (unadjusted OR: 2.03, 95% CI: 1.60–2.58, I
2=63%, P<0.00001; multivariate-adjusted OR: 2.00, 95% CI: 1.64–2.44, I
2=40%, P<0.00001). Further subgroup analysis did not find differences between different oliguria criteria or surgical types. Furthermore, the AKI group’s pooled intraoperative urine output was less (mean differences: −0.16, 95% CI: −0.26 to −0.07, P<0.001). Intraoperative oliguria was associated with increased demand for postoperative RRT (risk ratios: 4.71, 95% CI: 2.83–7.84, P<0.001) and in-hospital mortality (risk ratios: 1.83, 95% CI: 1.24–2.69, P=0.002), but not with prolonged length of hospital stay (mean differences: 0.55, 95% CI: −0.27 to 1.38, P=0.19).

Conclusions:

Intraoperative oliguria was significantly associated with a higher incidence of postoperative AKI, as well as increased in-hospital mortality and demand for postoperative RRT, but not with prolonged hospitalization.
MarioHeart: Novel In-Vitro Flow Model for Testing Heart Valve Prostheses and Anticoagulant Therapies
Authors: Devos Maxime , Liesdek Omayra C. D. , Suyker Willem J. L. , van Tuijl Sjoerd , Schutgens Roger E. G. , van de Vosse Frans N. , de Heer Linda M. , Rutten Marcel C. M.
Published: March 2023

Mechanical heart valve (MHV) prostheses present a risk of thromboembolic complications despite antithrombotic therapy. Further steps in the development of more hemocompatible MHVs and new anticoagulants are impeded due to the lack of adequate in-vitro models. With the development of a novel in-vitro model (MarioHeart), a pulsatile flow similar to the arterial circulation is emulated. The MarioHeart design owns unique features as 1) a single MHV within a torus with low surface/volume ratio, 2) a closed loop system, and 3) a dedicated external control system driving the oscillating rotational motion of the torus. For verification purposes, a blood analog fluid seeded with particles was used to assess fluid velocity and flow rate using a speckle tracking method on high-speed video recordings of the rotating model. The flow rate resembled the physiological flow rate in the aortic root, in both shape and amplitude. Additional in-vitro runs with porcine blood showed thrombi on the MHV associated with the suture ring, which is similar to the in-vivo situation. MarioHeart is a simple design which induces well-defined fluid dynamics resulting in physiologically nonturbulent flow without stasis of the blood. MarioHeart seems suitable for testing the thrombogenicity of MHVs and the potential of new anticoagulants.
Continuity and Change in Dao Yin: Comparing and Contrasting the Therapeutic Exercises in Yin Shu (The Book of Pulling, c. 2nd Century BCE) and Zhu Bing Yuan Hou Lun (Treatise on the Origins and Manifestations of Various Diseases, 610 CE)
Authors: Yang Dolly
Published: March 2023

The manuscript Yin Shu (The Book of Pulling), excavated from Zhangjiashan Han Tomb No. 247, is the earliest surviving text on therapeutic exercise known as Dao Yin (lit. guiding and pulling). Discovered in 1983, this Dao Yin text, together with the drawings of 44 figures performing “guiding and pulling” exercises found in the Mawangdui Han Tomb in 1974, are of great significance to the study of the early history of Dao Yin. Prior to these discoveries, researchers into Dao Yin relied mainly on material found in the Dao Zang (the Daoist Canon), compiled in 1145. This led to their conclusion that Dao Yin was essentially Daoist. The development of Dao Yin reached its zenith during the Sui Dynasty (581–618 CE), when it became one of the three medical departments at the imperial medical education institution. As part of the medical reform of the second Sui Emperor, Yang Di, Dao Yin became the treatment of choice, and the employment of a large number of Dao Yin specialists to the Sui court transformed the state medical service. The compilation of Zhu Bing Yuan Hou Lun (Treatise on the Origins and Manifestations of Various Diseases) under Yang Di’s decree, incorporated an abundance of resources on Dao Yin, enabling physicians to potentially “prescribe” Dao Yin to their patients. Situating both Yin Shu and Zhu Bing Yuan Hou Lun in their social and historical contexts, this article analyses their editorial treatments, examines their different objectives, styles, and readerships, and compares the various exercises described in the two texts. It emphasizes the fact that over a period of nearly a thousand years, from the late Warring States (475–221 BCE) to the Sui and Tang periods, Dao Yin was an important medical practice, culminating in its institutionalization by the Sui government.
“They Would Lift My Spirits”
Authors: Fisher Marlena C. , Parrillo Elaina , Petchler Claire , Kub Joan , Hughes Mark T. , Sulmasy Daniel P. , Baker Deborah , Nolan Marie T.
Published: March 2023

Surrogate decision-makers make critical decisions for loved ones at the end of life, and some experience lasting negative psychological outcomes. Understanding whom they rely on for support and the types of support they value may inform nursing care and that of other health team members who work with surrogates. The purpose of the study was to explore decision support and other types of support provided to surrogate decision-makers at the end of life of their loved one and perceived usefulness of the support. This secondary analysis of data from a mixed-methods study involved the examination of the transcripts of qualitative interviews with 13 surrogate decision-makers in the United States, conducted between 2010 and 2014. A constant comparative method was used to identify common themes surrounding surrogate decision support at the end of life. Surrogates valued advance directives and conversations with their loved one about treatment preferences. Surrogates described involving many different types of people in decision-making and other types of support. Finally, surrogates appreciated being reassured that they were doing a good job in making decisions and seemed to seek out this type of affirmation from various sources including the health care team, family, and friends. Nurses are well-positioned to provide this affirmation because of the time that they spend caring for the patient and family. Future research should further explore the concept of affirmation of surrogates in their role as a means of support as they make decisions for a loved one.
Correction of the High Fold in Difficult Secondary Blepharoplasty Through Retro-Orbicularis Oculi Fat Transposition and Augmentation in Asians
Authors: Wang Huili , Liu Ning , Li Xinxin , Zhu Ziwei , Wen Ting , Liu Yufeng
Published: March 2023

Background

Secondary blepharoplasty to correct a high crease is considered challenging for most surgeons, especially in patients who show overly excessive removal of eyelid tissue in Asians. Therefore, we define a typical difficult secondary blepharoplasty as when patients present too high eyelid fold with excessive tissue resection and preaponeurotic fat deficiency. This study provides the technique of retro-orbicularis oculi fat (ROOF) transferring and volume augmentation to reconstruct eyelid anatomical structure on the base of a series of difficult secondary blepharoplasty cases in Asians and assess the effectiveness of the method in the meanwhile.

Method

This was a secondary blepharoplasty cases–based retrospective observational study. From October 2016 to May 2021, a total of 206 cases were performed blepharoplasty revision surgery to correct high folds. Among them, a total of 58 cases (6 men, 52 women) diagnosed with difficult blepharoplasty were applied ROOF transferring and volume augmentation to correct high folds and were followed up on time. Depending on the distribution of ROOF of different thicknesses, we designed 3 different methods of harvesting and transferring ROOF flaps. The mean follow-up for patients in our study was 9 months, a range of 6 to 18 months. The postoperative results were reviewed, graded, and analyzed.

Result

Most patients (89.66%) were satisfied. No postoperative complications were observed, such as infection, dehiscence of incision, tissue necrosis, levator dysfunction, or multiple creases. The mean height of the mid, medial, and lateral eyelid folds decreased from 8.96 ± 0.43, 8.21 ± 0.58, and 7.96 ± 0.53 mm to 6.77 ± 0.55, 6.27 ± 0.57, and 6.65 ± 0.61 mm, respectively.

Conclusions

Retro-orbicularis oculi fat transposition or/and its enhancement contributes significantly to the reconstruction of the physiology of the eyelid structure and provides an available surgical option for the correction of too high folds in blepharoplasty.
Treatment of Chronic Hypertrophic Burn Scars With a Fractional CO2 Laser Is Well Tolerated in an Outpatient Clinic Setting
Authors: Donnellan Kimberly A. , Hinson Chandler S. , Blevins Addison C. , Weaver Katrina L. , Lintner Alicia C. , Butts Charles C. , Williams Ashley Y. , Lee Yann-leei L. , Simmons Jon D. , Bright Andrew C.
Published: March 2023

Introduction

The necessity of treating hypertrophic burn scars has expanded significantly with increased burn survivorship. Ablative lasers, such as carbon dioxide (CO2) lasers, have been the most common nonoperative option for improving functional outcomes in severe recalcitrant hypertrophic burn scars. However, the overwhelming majority of ablative lasers used for this indication require a combination of systemic analgesia, sedation, and/or general anesthesia due to the painful nature of the procedure. More recently, the technology of ablative lasers has advanced and is more tolerable than their first-generation counterparts. Herein, we hypothesized that refractory hypertrophic burn scars can be treated by a CO2 laser in an outpatient clinic.

Methods

We enrolled 17 consecutive patients with chronic hypertrophic burn scars that were treated with a CO2 laser. All patients were treated in the outpatient clinic with a combination of a topical solution (23% lidocaine and 7% tetracaine) applied to the scar 30 minutes before the procedure, Cryo 6 air chiller by Zimmer, and some patients received a mixture of N2O/O2. Laser treatments were repeated every 4 to 8 weeks until the patient's goals were met. Each patient completed a standardized questionnaire to assess tolerability and patient satisfaction of functional results.

Results

All patients tolerated the laser well in the outpatient clinic setting, with 0% indicating “not tolerable,” 70.6% “tolerable,” and 29.4% “very tolerable.” Each patient received more than 1 laser treatment for the following complaints: decreased range of motion (n = 16, 94.1%), pain (n = 11, 64.7%), or pruritis (n = 12, 70.6%). Patients were also satisfied with the results of the laser treatments (“no improvement or worsened” = 0%, “improved” = 47.1%, and “significant improvement” = 52.9%). The age of patient, type of burn, location of burn, presence of skin graft, or age of scar did not significantly affect the tolerability of treatment or satisfaction of outcome.

Conclusions

The treatment of chronic hypertrophic burn scars with a CO2 laser is well tolerated in an outpatient clinic setting in select patients. Patients reported a high level of satisfaction with notable improvement in functional and cosmetic outcomes.
Volumetric Analysis of Unilateral Alveolar Bone Defect Using Modified Subtraction in Older Chinese Patients
Authors: Li Kongying , Li Silei , Liu Bing , Wang Yongqian
Published: March 2023

A large number of older patients (≥13 y old) with alveolar clefts missed the optimal alveolar bone grafting time period in China. This study aimed to determine the accuracy and repeatability of modified computer-aided engineering subtraction for volumetric measurement of these patients. In addition, the study aimed to determine whether the volume of defect is correlated with cleft type (cleft lip and alveolus, cleft lip and palate), cleft location, age, and sex. Preoperative computed tomography data from 100 patients of unilateral alveolar cleft patients without secondary alveolar bone grafting were measured using 2 methods. The maxillary resin model around the alveolar cleft was printed using the 3-dimensional (D) printing method, and the volume of the defect was measured using the drainage method. In the modified subtraction method, Mimics software was used to simulate fracture filling by layer drawing, and the defect volume was determined by subtracting the preoperative fracture template from the filled 3D skull template. The mean time taken to calculate an alveolar cleft defect volume by modified subtraction method was 3.2 minutes. The average defect volume measured using the 3D printing and modified subtraction methods were 1.58±0.41 and 1.55±0.42 cm3, respectively. Findings suggest that cleft location and age do not affect the defect volume of older patients with alveolar cleft, unlike cleft type and sex. The modified computer-aided subtraction method provides good accuracy, consistency, and reproducibility in measuring alveolar ridge defect volume. Moreover, this method is more efficient and cost-effective than the 3D-printed model method.
Large Lipoma of the Lateral Space of the Neck
Authors: Tabaković Saša Z. , Tabaković Zoran S.
Published: March 2023

Giant lipoma is characterized by asymptomatic growth and compared with other parts of the body rarely occurs on the neck. If the tumor is localized in the lateral segment of the neck, it can show symptoms in the form of dysphagia and dyspnea. Preoperatively, it is important to perform computed tomography (CT) diagnostic to determine the size of the lesion and makes the plan for operative treatment. The paper presents the case of a 66-year-old patient with a tumor in the neck area as well as swallowing disorders and suffocation during sleep. Palpation revealed a tumor of soft consistency, and based on a CT scan of the neck, the differential diagnosis confirmed giant lipoma. Clinical picture and CT findings of giant neck lipoma are clear in most cases. Due to the atypical localization and size, the tumor should be removed to prevent possible functional disturbances. The treatment is operative, and a histopathological examination should exclude malignancy.
Implementation of Staging Guidelines in Early Esophageal Cancer
Authors: Reza Joseph A. , Raman Vignesh , Vekstein Andrew , Grau-Sepulveda Maria , Burfeind William P. , Chin Kristine , Petrov Roman , Erkmen Cherie P.
Published: March 2023

Objective:

To evaluate the adoption and clinical impact of endoscopic resection (ER) in early esophageal cancer.

Background:

Staging for early esophageal cancer is largely inaccurate. Assessment of the impact of ER on staging accuracy is unknown, as is the implementation of ER.

Methods:

We retrospectively reviewed 2608 patients captured in the Society of Thoracic Surgeons General Thoracic Surgery Database between 2015 and 2020. Patients with clinical T1 and T2 esophageal cancer without nodal involvement (N0) who were treated with upfront esophagectomy were included. Staging accuracy was assessed by clinical-pathologic concordance among patients staged with and without ER. We also sought to measure adherence to National Comprehensive Cancer Network staging guidelines for esophageal cancer staging, specifically the implementation of ER.

Results:

For early esophageal cancer, computed tomography/positron emission tomography/endoscopic ultrasound (CT/PET/EUS) accurately predicts the pathologic tumor (T) stage 58.5% of the time. The addition of ER to staging was related to a decrease in upstaging from 17.6% to 10.8% (P=0.01). Adherence to staging guidelines with CT/PET/EUS improved from 58.2% between 2012 and 2014 to 77.9% between 2015 and 2020. However, when ER was added as a staging criterion, adherence decreased to 23.3%. Increased volume of esophagectomies within an institution was associated with increased staging adherence with ER (P=0.008).

Conclusions:

The use of CT/PET/EUS for the staging of early esophageal cancer is accurate in only 56.3% of patients. ER may increase staging accuracy as it is related to a decrease in upstaging. ER is poorly utilized in staging of early esophageal cancer. Barriers to the implementation of ER as a staging modality should be identified and corrected.
The final decision among the injured elderly, to stop or to continue? Predictors of withdrawal of life supporting treatment
Authors: Bhogadi Sai Krishna , Magnotti Louis J. , Hosseinpour Hamidreza , Anand Tanya , El-Qawaqzeh Khaled , Nelson Adam , Colosimo Christina , Spencer Audrey L. , Friese Randall , Joseph Bellal
Published: March 2023

BACKGROUND

There is a paucity of data on factors that influence the decision regarding withdrawal of life supporting treatment (WLST) in geriatric trauma patients. We aimed to identify predictors of WLST in geriatric trauma patients.

METHODS

This retrospective analysis of the American College of Surgeons- Trauma Quality Improvement Program (2017–2019) included all severely injured (Injury Severity Score >15) geriatric trauma patients (≥65 years). Multivariable logistic regression was performed to identify independent predictors of WLST.

RESULTS

There were 155,583 patients included. Mean age was 77 ± 7 years, 55% were male, 97% sustained blunt injury, and the median Injury Severity Score was 17 [16–25]. Overall WLST rate was 10.8%. On MLR analysis, increasing age (adjusted odds ratio [aOR], 1.35; 95% confidence interval [CI], 1.33–1.37; p < 0.001), male sex (aOR, 1.14; 95% CI, 1.09–1.18; p < 0.001), White race (aOR, 1.44; 95% CI, 1.36–1.52; p < 0.001), frailty (aOR, 1.42; 95% CI, 1.34–1.50; p < 0.001), government insurance (aOR, 1.27; 95% CI, 1.20–1.33; p < 0.001), presence of advance directive limiting care (aOR, 2.55; 95% CI, 2.40–2.70; p < 0.001), severe traumatic brain injury (aOR, 1.80; 95% CI, 1.66–1.95; p < 0.001), ventilator requirement (aOR, 12.73; 95% CI, 12.09–13.39; p < 0.001), and treatment at higher level trauma centers (Level I aOR, 1.49; 95% CI, 1.42–1.57; p < 0.001; Level II aOR, 1.43; 95% CI, 1.35–1.51; p < 0.001) were independently associated with higher odds of WLST.

CONCLUSION

Our results suggest that nearly one in 10 severely injured geriatric trauma patients undergo WLST. Multiple patient and hospital related factors contribute to decision making and directed efforts are necessary to create a more standardized process.

LEVEL OF EVIDENCE

Prognostic and Epidemiological; Level III.
Conserving Biodiversity in Coffee Agroecosystems: Insights from a Herpetofauna Study in the Colombian Andes with Sustainable Management Proposal
Authors: Ríos-Orjuela Juan Camilo , Falcón-Espitia Nelson , Arias-Escobar Alejandra , Plazas-Cardona Dennys
Published: March 2023

Amphibians and reptiles are important indicators of ecosystem health, yet their populations are declining worldwide due to habitat loss and climate change. Agroecosystems, such as coffee plantations, can provide important habitat for these species. We conducted field surveys in the Sumapaz region of Colombia to identify the microclimatic variables that influence the diversity and abundance of herpetofauna in coffee crops. The canonical correspondence analysis revealed that leaf litter abundance, crop area, and age category were the most important structural variables for determining herpetofauna diversity. Our findings suggest that coffee plantations function similarly to secondary vegetation, and maintaining a thick layer of leaf litter is critical for establishing complex and structured animal communities. This study proposes a set of sustainable agricultural management principles to promote the existence of amphibians and reptiles in coffee crops. By adopting these practices, it is possible to prevent the decline in the population of amphibians and reptiles due to the expansion of the agricultural frontier, as seen in other coffee-growing regions. The findings of this study contribute to a better understanding of how to balance agricultural production and biodiversity conservation in the context of agroecosystems.

*Una versión en español de este documento puede ser encontrada como material suplementario/ a Spanish version of this paper can be found as supplementary material.
Spinal Cord Stimulation using time-dynamic pulses achieves faster and longer reversal of allodynia compared to tonic pulses in a rat model of neuropathic pain
Authors: Edhi Muhammad , Zhu Changfang , Jeong Ki-Soo , Rogness Victoria , Esteller Rosana , Saab Carl
Published: March 2023

Spinal cord stimulation (SCS) utilizing time-dynamic pulses (TDPs) is an emergent field of neuromodulation that continuously and automatically modulates pulse parameters. We previously demonstrated that TDPs delivered for 60 min at sub-paresthesia amplitudes significantly reversed allodynia in a rat model of neuropathic pain. Because we observed these anti-allodynic effects persisted post-cessation, we investigated the extended temporal dynamics of SCS-induced analgesia. We hypothesized that TDPs achieve a longer duration of analgesia than tonic stimulation. Both TDPs and tonic stimulation reversed PWT to near pre-chronificiation levels within 30 minutes. Most TDPs exhibited significantly slower ramp-up slope (analgesia ‘wash-in’ rates) compared to tonic stimulation (amplitude modulation: 0.16±0.03 min-1, pulse width modulation: 0.18±0.05 min-1, stochastic modulation: 0.17±0.04 min-1, tonic: 0.31±0.06 min-1). All TDPs showed slower wind-down slopes (analgesia ‘wash-out’ rates) compared to tonic (-0.29±0.07 min-1), with pulse width modulation (-0.11±0.02 min-1) reaching significance. Extending SCS from 60 to 90 minutes revealed all TDPs maintain analgesic efficacy longer than tonic stimulation, which decreased significantly at both 75 and 90 minutes (from 13.8±0.5 g to 12.3±0.9 g and to 11.0±0.5 g, respectively). Although TDPs and tonic stimulation comparably mitigated allodynia, TDPs generally exhibited slower temporal dynamics, suggesting longer-lasting analgesic effects and potentially different mechanisms of action.
InstaPrism: an R package for fast implementation of BayesPrism
Authors: Hu Mengying , Chikina Maria
Published: March 2023

Computational cell-type deconvolution is an important analytic technique for modeling the compositional heterogeneity of bulk gene expression data. A conceptually new Bayesian approach to this problem, BayesPrism, has recently been proposed and has subsequently been shown to be superior in accuracy and robustness against model misspecifications by independent studies. However, given that BayesPrism relies on Gibbs sampling, it is orders of magnitude more computationally expensive than standard approaches. Here, we introduce the InstaPrism algorithm which re-implements BayesPrism in a derandomized framework by replacing the time-consuming Gibbs sampling steps in BayesPrism with a fixed-point algorithm. We demonstrate that the new algorithm is effectively equivalent to BayesPrism while providing a considerable speed advantage. InstaPrism is implemented as a standalone R package with C++ backend.
Drosophilaantennae are dispensable for gravity orientation
Authors: Kladt Nikolay , Reiser Michael B.
Published: March 2023

The nearly constant downward force of gravity has powerfully shaped the behaviors of many organisms [1]. Walking flies readily orient against gravity in a behavior termed negative gravitaxis. InDrosophilathis behavior is studied by observing the position of flies in vials [2–4] or simple mazes [5–9]. These assays have been used to conduct forward-genetic screens [5, 6, 8] and as simple tests of locomotion deficits [10–12]. Despite this long history of investigation, the sensory basis of gravitaxis is largely unknown [1]. Recent studies have implicated the antennae as a major mechanosensory input [3, 4], but many details remain unclear. Fly orientation behavior is expected to depend on the direction and amplitude of the gravitational pull, but little is known about the sensitivity of flies to these features of the environment. Here we directly measure the gravity-dependent orientation behavior of flies walking on an adjustable tilted platform, that is inspired by previous insect studies [13–16]. In this arena, flies can freely orient with respect to gravity. Our findings indicate that flies are exquisitely sensitive to the direction of gravity’s pull. Surprisingly, this orientation behavior does not require antennal mechanosensory input, suggesting that other sensory structures must be involved.
Neural and computational underpinnings of biased confidence in human reinforcement learning
Authors: Ting Chih-Chung , Salem-Garcia Nahuel , Palminteri Stefano , Engelmann Jan B. , Lebreton Maël
Published: March 2023

While navigating a fundamentally uncertain world, humans and animals constantly produce subjective confidence judgments, thereby evaluating the probability of their decisions, actions or statements being correct. Confidence typically correlates with neural activity positively in a ventromedial-prefrontal (VMPFC) network and negatively in a dorsolateral and dorsomedial prefrontal network. Here, combining fMRI with a reinforcement-learning paradigm, we leverage the fact that humans are more confident in their choices when seeking gains than avoiding losses to reveal a functional dissociation: whereas the dorsal prefrontal network correlates negatively with a condition-specific confidence signal, the VMPFC network positively encodes task-wide confidence signal incorporating the valence-induced bias. Challenging dominant neuro-computational models, we found that decision-related VMPFC activity better correlates with confidence than with option-values inferred from reinforcement-learning models. Altogether, these results identify the VMPFC as a key node in the neuro-computational architecture that builds global feeling-of-confidence signals from latent decision variables and contextual biases during reinforcement-learning.
Early functional connectivity alterations in contralesional motor networks influence outcome after severe stroke
Authors: Braaß Hanna , Gutgesell Lily , Backhaus Winifried , Higgen Focko L. , Quandt Fanny , Choe Chi-un , Gerloff Christian , Schulz Robert
Published: March 2023

Connectivity studies have significantly extended the knowledge on motor network alterations after stroke. Compared to interhemispheric or ipsilesional networks, changes in the contralesional hemisphere are poorly understood. Data obtained in the acute stage after stroke and in severely impaired patients are remarkably limited. This study aimed to investigate early functional connectivity changes of the contralesional parieto-frontal motor network and their relevance for the functional outcome after severe motor stroke. Resting-state functional imaging data were acquired in 19 patients within the first two weeks after severe stroke. Nineteen healthy participants served as a control group. Functional connectivity was calculated from five key motor areas of the parieto-frontal network on the contralesional hemisphere as seed regions and compared between the groups. Connections exhibiting stroke-related alterations were correlated with clinical follow-up data obtained after 3 to 6 months. The main finding was an increase in coupling strength between the contralesional supplementary motor area and the sensorimotor cortex. This increase was linked to persistent clinical deficits at follow-up. Thus, an upregulation in contralesional motor network connectivity might be an early pattern in severely impaired stroke patients. It might carry relevant information regarding the outcome which adds to the current concepts of brain network alterations and recovery processes after severe stroke.
MicroCT-based imaging of microvasculature within bone and peri-implant tissues
Authors: Haberthür David , Khoma Oleksiy-Zakhar , Hoessly Tim , Zoni Eugenio , Julio Marianna Kruithof-de , Ryan Stewart D. , Grunewald Myriam , Bellón Benjamin , Sandgren Rebecca , Handschuh Stephan , Pippenger Benjamin E. , Bosshardt Dieter , Djonov Valentin , Hlushchuk Ruslan
Published: March 2023

Abstract

Angiogenesis is essential for skeletal development, bone healing, and regeneration. Improved non-destructive, three-dimensional (3D) imaging of the vasculature within bone tissue would benefit many research areas, especially implantology and tissue engineering.

X-ray microtomography (microCT) is a well-suited non-destructive 3D imaging technique for bone morphology. For microCT-based detection of vessels, it is paramount to use contrast enhancement. Limited differences in radiopacity between perfusion agents and mineralized bone make their distinct segmentation problematic and have been a major drawback of this approach. A decalcification step resolves this issue but inhibits the simultaneous assessment of bone microstructure and vascular morphology. The problem of contrasting becomes further compounded in samples with metal implants.

This study describes μAngiofil-enhanced microCT-based visualization of vasculature within bone tissue in small and large animal models, with and without decalcification. We present simultaneous microvascular and bone imaging in murine tibia, a murine bone metastatic model, the pulp chamber, gingiva, and periodontal ligaments. In a large animal model (minipig), we perform visualization and segmentation of different tissue types and vessels in the hemimandible containing metal implants. Moreover, we show the potential of the dual-energy approach in facilitating the distinction between bone tissue and the applied contrast agent.

Our manuscript introduces the first non-destructive approach for 3D imaging of the vasculature within soft and hard tissues in the vicinity of metal implants in a large animal model.
Destabilization of neuromuscular junctions and deregulation of activity-dependent signalling pathways in Myotonic Dystrophy type I
Authors: Falcetta Denis , Quirim Sandrine , Cocchiararo Ilaria , Cornut Mélanie , Théodore Marine , Stiefvater Adeline , Lin Shuo , Tintignac Lionel , Ivanek Robert , Kinter Jochen , Rüegg Markus A. , Sinnreich Michael , Castets Perrine
Published: March 2023

Myotonic Dystrophy type I (DM1) is the most common muscular dystrophy in adults. Previous reports have highlighted that neuromuscular junctions (NMJs) deteriorate in skeletal muscle from DM1 patients and mouse models thereof. However, the underlying pathomechanisms and their contribution to muscle dysfunction remain unknown. We compared changes in NMJs and activity-dependent signalling pathways inHSALRandMbnl1ΔE3/ΔE3mice, two established mouse models for DM1. DM1 muscle showed major deregulation of calcium/calmodulin-dependent protein kinases II (CaMKIIs), which are key activity sensors regulating synaptic gene expression and acetylcholine receptor (AChR) recycling at the NMJ. Both mouse models displayed increased fragmentation of the endplate, which preceded muscle degeneration. Endplate fragmentation was not accompanied by changes in AChR turnover at the NMJ. However, expression of synaptic genes was up-regulated in DM1 muscle, which may be linked to the abnormally high activity of histone deacetylase 4 (HDAC4), a known target of CaMKII. Consistently, expression of myosin heavy chains was deregulated as well, leading to a major switch to type IIA fibres inMbnl1ΔE3/ΔE3muscle, and to a lesser extent inHSALRmuscle. Interestingly, although HDAC4 was efficiently induced upon nerve injury, synaptic gene up-regulation was abrogated in DM1 muscle, together with a reduced increase in AChR turnover. This suggested that HDAC4-independent mechanisms lead to the defective response to denervation in DM1 muscle. Our study shows that activity-dependent signalling pathways are disturbed in DM1 muscle, which may contribute to NMJ destabilization and muscle dysfunction in DM1 patients.
Gene-level alignment of single cell trajectories
Authors: Sumanaweera Dinithi , Suo Chenqu , Cujba Ana-Maria , Muraro Daniele , Dann Emma , Polanski Krzysztof , Steemers Alexander S. , Lee Woochan , Oliver Amanda J. , Park Jong-Eun , Meyer Kerstin B. , Dumitrascu Bianca , Teichmann Sarah A.
Published: March 2023

Single-cell data analysis can infer dynamic changes in cell populations, for example across time, space or in response to perturbation. To compare these dynamics between two conditions, trajectory alignment via dynamic programming (DP) optimization is frequently used, but is limited by assumptions such as a definite existence of a match. Here we describeGenes2Genes, a Bayesian information-theoretic DP framework for aligning single-cell trajectories.Genes2Genesovercomes current limitations and is able to capture sequential matches and mismatches between a reference and a query at single gene resolution, highlighting distinct clusters of genes with varying patterns of expression dynamics. Across both real world and simulated datasets,Genes2Genesaccurately captured different alignment patterns, demonstrated its utility in disease cell state trajectory analysis, and revealed that T cells differentiatedin vitromatched to an immaturein vivostate while lacking expression of genes associated with TNFɑ signaling. This use case demonstrates that precise trajectory alignment can pinpoint divergence from thein vivosystem, thus guiding the optimization ofin vitroculture conditions.
Brain structure-function relationships across the human lifespan based on network eigenmodes
Authors: Yang Yaqian , Tang Shaoting , Wang Xin , Zhen Yi , Zheng Yi , Zheng Hongwei , Liu Longzhao , Zheng Zhiming
Published: March 2023

While brain function is considered to be tightly supported by the underlying structure, the connectome-based link estimated by current models is relatively moderate, leaving the structure-function relationship an ongoing challenge in neuroscience. Here, by proposing a novel mapping method based on network eigendecomposition, we present a concise and strong correspondence between structure and function. We show that the explanation of functional connectivity can be significantly improved by incorporating interactions between different structural eigenmodes, highlighting the potential importance of collective, higher-order coupling patterns between structure and function. We also demonstrate the pronounced advantage of the present mapping in capturing individual-specific information, and apply it to assess individual differences of structure-function coupling across the lifespan. We find that structure-function liberality weakens with age, which is driven by the decreases in functional components that are less constrained by anatomy, while the magnitude of structure-aligned components is preserved. Our results contribute to a more refined understanding of structure-function coupling and how it evolves with age.