bluuebunny/crossref_metadata_2025 huggingface dataset:
Pumping for Two: Pregnancy in Patients Supported With a Left Ventricular Assist Device
Authors: Oren Daniel , Moeller Cathrine M. , Haythe Jennifer H. , Rubinstein Gal , Fernandez Valledor Andrea , Lotan Dor , Rosenblum Hannah , Colombo Paolo C. , Yuzefpolskaya Melana , Topkara Veli K. , Clerkin Kevin J. , Raikhelkar Jayant K. , Fried Justin A. , Naka Yoshifumi , Takeda Koji , Latif Farhana , Sayer Gabriel , Uriel Nir
Published: November 2023

This review discusses the challenges and outcomes associated with pregnancy during left ventricular assist device (LVAD) support. Women account for a third of the heart failure population in the United States. Left ventricular assist devices have emerged as a safe and effective treatment option for patients with advanced heart failure. Pregnancy during LVAD support can occur, and it presents significant risks to both mother and fetus, including hemodynamic stress, thrombotic events, medication-associated teratogenicity, and uterine impingement. This literature review identified 10 cases of confirmed pregnancy during LVAD support, of which eight resulted in successful births. Maternal and fetal mortality occurred in one case, and there was a spontaneous abortion in one case. The review highlights the importance of a multidisciplinary approach, promotion of shared decision-making, thoughtful anticoagulation, adjustment of LVAD speed, and medication optimization to maintain hemodynamic support during pregnancy. Hemodynamic changes during pregnancy include increased cardiac output, heart rate, and plasma volume, as well as decreased systemic vascular resistance, which can impact LVAD support. Despite reduced pulsatility in LVAD-supported patients, ovulation and reproductive capacity might be preserved, and viable pregnancies may be achieved with appropriate management. The review provides insights into the risks and considerations for a viable pregnancy during LVAD support, including the need for ongoing research to inform joined decision-making.
A Mortality Prediction Score for Patients With Veno-Venous Extracorporeal Membrane Oxygenation (VV-ECMO): The PREDICT VV-ECMO Score
Authors: Rilinger Jonathan , Book Rebecca , Kaier Klaus , Giani Marco , Fumagalli Benedetta , Jäckel Markus , Bemtgen Xavier , Zotzmann Viviane , Biever Paul M. , Foti Giuseppe , Westermann Dirk , Lepper Philipp M. , Supady Alexander , Staudacher Dawid L. , Wengenmayer Tobias
Published: November 2023

Mortality prediction for patients with the severe acute respiratory distress syndrome (ARDS) supported with veno-venous extracorporeal membrane oxygenation (VV-ECMO) is challenging. Clinical variables at baseline and on day 3 after initiation of ECMO support of all patients treated from October 2010 through April 2020 were analyzed. Multivariate logistic regression analysis was used to identify score variables. Internal and external (Monza, Italy) validation was used to evaluate the predictive value of the model. Overall, 272 patients could be included for data analysis and creation of the PREDICT VV-ECMO score. The score comprises five parameters (age, lung fibrosis, immunosuppression, cumulative fluid balance, and ECMO sweep gas flow on day 3). Higher score values are associated with a higher probability of hospital death. The score showed favorable results in derivation and external validation cohorts (area under the receiver operating curve, AUC derivation cohort 0.76 [95% confidence interval, CI, 0.71–0.82] and AUC validation cohort 0.74 [95% CI, 0.67–0.82]). Four risk classes were defined: I ≤ 30, II 31–60, III 61–90, and IV ≥ 91 with a predicted mortality of 28.2%, 56.2%, 84.8%, and 96.1%, respectively. The PREDICT VV-ECMO score suggests favorable performance in predicting hospital mortality under ongoing ECMO support providing a sound basis for further evaluation in larger cohorts.
Should endoscopic laser excision be offered as the first-line management for patients with eroded mesh? Outcomes of a systematic review of literature
Authors: Ripa Francesco , Enikeev Dmitry , Talyshinskii Ali , Juliebø-Jones Patrick , Tzelves Lazaros , Kallidonis Panagiotis , Somani Bhaskar
Published: November 2023

Purpose of review

Mesh erosions following previous synthetic sling/mesh surgery for stress urinary incontinence (SUI) have become increasingly common. This systematic review provides evidence for the role of laser excision as a first-line management in patients with eroded mesh.

Recent findings

Fourteen articles (173 patients) were included for the final review. Among these, 138 patients (79.8%) were submitted to trans-urethral laser excision of eroded urethral/bladder mesh over a median time to presentation of 36.6 months. Over a median follow-up of 23.6 months, 88 (63.7%) reported a complete resolution, 32 (23.2%) reported persistence or recurrence of SUI and 17 (12.3%) presented with recurrent mesh erosion. The success rate after a single endoscopic procedure was 66.5, vs. 93.5% after additional endoscopic procedures, with only 9 (6.6%) requiring open surgical excision. Overall, there were seven (5.1%) postoperative complications including two urethrovaginal fistulas, two UTIs and haematuria each, and one case of urethral diverticulum.

Laser excision of eroded mid-urethral slings into either the bladder or urethra is a challenging complication of minimally invasive incontinence surgery. Laser excision was able to achieve a good success rate with single or staged endoscopic procedure with a low risk of complication. It represents a valid first treatment option, although patients should be managed in mesh referral centres in collaboration with uro-gynaecology teams.
CEP55, serving as a diagnostic marker gene for osteosarcoma, triggers the JAK2-STAT3-MMPs axis
Authors: Yan Yiqun , He Junyan , Cheng Wendan
Published: November 2023

Background:

Osteosarcoma (OS) stands as the prevailing form of primary bone cancer in clinical practice. Lack of effective treatment options and an overall poor prognosis are caused by the disease’s exceptionally rare occurrence and unclear rationale.

Objective:

This study’s goal is to determine diagnostic marker genes involved in the progression of OS and investigate related pathways and mechanisms with the purpose of offering effective methods for OS diagnostics and therapy.

Methods:

The Gene Expression Omnibus database provided the gene microarray data. Core genes were identified through differential expression analysis and WGCNA. Three techniques for machine learning, random forest, least absolute shrinkage and selection operator regression, and support vector machine recursive feature elimination, were used to further screen the core genes and obtain diagnostic marker genes for OS. The specificity and sensitivity of the diagnostic marker genes for OS diagnosis were evaluated using receiver operating characteristic curves. Western blotting analysis was used for preliminary validation of the diagnostic marker genes and their related pathways.

Results:

Two diagnostic marker genes were identified through screening, including CEP55 and VWF. Receiver operating characteristic curves have been utilized to assess the diagnostic and therapeutic effects of CEP55 and VWF on OS. Western blotting analysis preliminarily validated the overexpression of CEP55 in OS and its capacity to control MMP2 and MMP9 levels by activating the JAK2/STAT3 signaling pathway.

Conclusion:

At the first time, this research shows that CEP55 and VWF are more powerful diagnostic and predictive indicators for OS. CEP55 holds the capacity to activate the JAK2/STAT3 signaling pathway and modulate MMP2 and MMP9 levels, thereby positioning it as a promising target in OS treatment.
Preventive Practices and Knowledge of Human Papillomavirus in Mayer-Rokitansky-Küster-Hauser (MRKH) Syndrome Individuals
Authors: Shim Jessica , Boskey Elizabeth R. , Lossie Amy , Staffa Steven J. , Grimstad Frances W.
Published: November 2023

Mayer-Rokitansky-Küster-Hauser syndrome (MRKH) is a congenital disorder typified by an underdeveloped female reproductive tract. An exploratory online survey of adults with MRKH found that many did not recall receiving the HPV vaccine, and answers to knowledge questions suggested inadequate HPV counseling. However, recalled vaccine counseling was associated with improved uptake.
Mapping Online Community Spaces through Online Focus Group Discussions among GBMSM in Guangdong, China: Implications for HIV/STD Prevention Services
Authors: Tan Rayner Kay Jin , Marley Gifty , Wang Tong , Li Chunyan , Byrne Margaret Elizabeth , Mu Rong , Tang Qiwen , Ramaswamy Rohit , Wang Cheng , Tang Weiming , Tucker Joseph D.
Published: November 2023

Background

Chinese gay, bisexual and other men who have sex with men (GBMSM) face discrimination in many facility-based health services, thus increasing the importance of online engagement. The purpose of this study was to examine online GBMSM community spaces and implications for HIV/STD prevention services.

Methods

We conducted a total of six online focus group discussions with Chinese GBMSM from Guangdong province on the chat-based platform WeChat in 2021. Focus group discussions were asynchronous, and participants were able to provide and map out online spaces that they had participated in and share their perspectives on online engagement. Data were analyzed through framework analysis.

Results

Overall, 48 participants participated. Most were mainly sexually attracted to men (n = 43, 90.0%), and never participated in in-person LGBTQ-related events (n = 29, 60.4%). Participants articulated a typology of online spaces along the axes of whether such spaces were Chinese platforms (vs. non-Chinese) or whether they were GBMSM-specific (vs. non-GBMSM-specific). Participants articulated several advantages of online spaces, including greater anonymity, opportunities for community building, sharing of sexual health information and being able to meet other GBMSM more efficiently. Drawbacks included the lack of personal connection, lack of safety measures for youth, encountering deception and the use of fake profile pictures, and needing a virtual proxy network to access some websites. Participants provided suggestions to further improve their experiences of online spaces.

Conclusions

While broad-based, GBMSM-specific messaging can be implemented in Chinese, GBMSM-specific spaces, sexual health messaging may also reach niche GBMSM communities in a variety of non-GBMSM spaces.
Predictors of long-term pain and function in individuals who received a custom dynamic orthosis and device-centric care pathway
Authors: Williamson Jared N. , Grunst Megan M. , Lynn Jeffrey , Williamson Gary A. , Blanck Ryan V. , Wilken Jason M.
Published: November 2023

Introduction:

Carbon fiber custom dynamic orthoses (CDOs) have been shown to effectively reduce pain and improve function in military service members with lower-limb impairment, but data are limited for civilians.

Objectives:

To evaluate the long-term outcomes of individuals who completed a CDO-centric care pathway in a civilian clinic by comparing baseline pain, mobility, and function with outcomes at long-term follow-up. To identify baseline characteristics and postintervention outcomes predictive of outcomes at long-term follow-up.

Methods:

Records of 131 adult patients who received a CDO and CDO-centric training were reviewed. Patient-reported measures of pain and physical function and timed assessment of walking and agility collected during routine clinical care were extracted. These patients were contacted on average 4 (±1) years postintervention to complete a survey including measures of pain and physical function.

Results:

The 63 participants who responded reported improved or greatly improved function, maximum pain, and typical pain on average, irrespective of age or sex (P < 0.001). Change in function from baseline to long-term follow-up was predicted by short-term change in function (35.1% of the variance; P < 0.001). Change in pain from baseline to long-term follow-up was predicted by baseline typical pain and change in four square step test time (63% of variance; P < 0.001).

Conclusions:

Most survey respondents reported positive outcomes. Long-term pain reduction and improved function were predicted by baseline status and by short-term changes associated with receiving a CDO and completing an intensive training program.
Large Bladder Stone Detected on Renal Scintigraphy
Authors: Deng Yan , Su Juan , Liu Zhaohui , Zhang Wei , Lei Xiaoping
Published: November 2023

A 39-year-old woman with hydronephrosis underwent99mTc-DTPA renal dynamic scintigraphy to evaluate renal function. The images revealed a central photopenic region in the urinary bladder. SPECT/CT images suggested the abnormal tracer distribution corresponding to a large urinary bladder stone.
Robin Sequence Facial Profile After Conservative Treatment: A Long-Term Follow-Up
Authors: Siqueira Gabriela Leticia Clavisio , Tonello Cristiano , Peixoto Adriano Porto , Daskalogiannakis John , Garib Daniela Gamba , Marques Ilza Lazarini , Ceide Roseli Zechi , Alonso Nivaldo , Ozawa Terumi Okada
Published: November 2023

Introduction:

Robin sequence (RS) is a congenital clinical condition characterized by micrognathia, glossoptosis, and respiratory distress. Conservative methods could be responsible for releasing feeding and respiratory impairment but little information about mandibular growth is known in long-term follow-up.

Objective:

Assessing the longitudinal behavior of the facial profile of individuals with isolated RS who underwent conservative micrognathia treatment using photographs during the whole craniofacial growth.

Methods:

Photographs of the right facial profile of 100 patients were used (50 individuals with isolated RS and 50 individuals without craniofacial anomaly). The individuals with RS were evaluated at 3 different times (T1: infant, T2: mixed dentition, T3: permanent dentition) by measuring the facial convexity angle (FCA; G.Sn.Pog´). A comparison between T3 and control group (C), individuals without craniofacial anomalies and in permanent dentition, was also performed, checking the FCA, nasolabial angle (Ls.Sn.Cm), mentolabial fold (Li.Si.Pog´), facial inferior third (Sn.Gn´.C) angles and the ratio between middle anterior facial height and lower anterior facial height.

Results:

The T3 group showed an increased angle of facial convexity and increased facial inferior third angle and middle anterior facial height/lower anterior facial height ratio compared with the control group. In the longitudinal evaluation of individuals with isolated RS, significant differences were identified between T1 and T2 groups and T1 and T3 groups showing that the increased facial convexity was higher in the infants and that did not change significantly between the phases of mixed and permanent dentition.

Conclusions:

RS showed increased facial convexity in all phases evaluated, but their convexity decreased with growth. When compared with individuals without craniofacial anomalies, the individuals continue to exhibit retrognathism in the permanent dentition. The lack of a mandible projection has led to a considerable number of orthognathic surgeries for the correction of discrepancies.
Correction of Cicatricial Lower Eyelid Retraction and Entropion With Combined Scar Release, Hard Palate Graft, and Lateral Canthal Suspension
Authors: Zhang Zhenzhen , Yanjun Sun , Ye Xinhai
Published: November 2023

Objective:

This study aimed to evaluate the outcome of a technique-combined scar release, hard palate spacer graft with the recession of the lower eyelid retractors, lateral canthal suspension in the repair of cicatricial lower eyelid retraction, and entropion.

Methods:

Records of 12 patients with cicatricial lower eyelid retraction and entropion who underwent the surgery from January 2019 to August 2021 were reviewed. Surgical techniques include the following procedures: release of scar, hard palate graft with recession of the lower eyelid retractors, and lateral canthal tightening to strengthen the support of the lower eyelid. The follow-up period was at least 12 months. Postoperative outcomes were evaluated by the improvement of lower eyelid retraction, resolution of eyelid entropion, and complications.

Results:

All patients showed resolution in lower lid entropion, and lower eyelid retraction was significantly improved with a mean elevation of 2.93±0.82 mm. None of the patients had severe complications postoperatively, and both ocular surface symptoms and cosmetic appearance were significantly improved.

Conclusions:

The technique achieves long-term stable outcomes in cicatricial lower lid retraction and entropion repair with a low morbidity rate.
A Method for Precise Reduction of Facial Bone Fractures Using Intraoperative Ultrasound With a Solid Gel Pad as a Coupling Medium
Authors: Kim Young Geun , Ryu Jeong-Ho , Lee Keun-Cheol
Published: November 2023

This study introduces a method to overcome technical challenges in using intraoperative ultrasound for the closed reduction of nasal bone and zygomatic arch fractures. The curvature of the face makes it difficult to apply an ultrasound probe to the facial area. We used a solid gel pad as a coupling medium during surgery to improve the scanning of facial bone fractures. The results show that the fracture sites observed on preoperative computed tomography scans can be easily visualized using intraoperative ultrasound, and real-time manipulation confirms successful reduction. The solid gel pad is light, malleable, easy to use, and provides accurate images. Overall, the use of ultrasound with a solid gel pad enhances the accuracy of closed reduction in facial bone fracture surgeries, confirming fracture patterns and ensuring precise reduction.
Postrhinoplasty Nasal Radix Cyst Treated with Endoscopic Marsupialization
Authors: Kwon Ha Gyung , Kim Jung Soo , Heo Sung Jae
Published: November 2023

Postrhinoplasty nasal radix cyst is a rare late complication, with few cases being reported in the literature. The appropriate treatment for this cyst is surgical removal. To date, an open approach or intracartilagenous incision has been performed in most cases. Herein, we present a case of a 68-year-old man with a bulging mass of radix who visited our clinic. The patient underwent open surgery for the mass, but the mass recurred 2 years after surgery. Although removal using the open approach was planned as in the previous surgery, marsupialization was performed because a connection with the frontal recess was seen on a computed tomography scan. We report a rare case of nasal radix cyst successfully treated with marsupialization without an external scar.
Sphenoid Sinus Foreign Body After Le Fort I Osteotomy
Authors: Moroi Akinori , Iguchi Ran , Yoshizawa Kunio , Ueki Koichiro
Published: November 2023

This report describes a rare case of a foreign body in the sphenoid sinus from the tip of an osteotome, which was lodged during the Le Fort I osteotomy. After surgery, a 2-mm-diameter round-shaped foreign body was seen as an opaque image in the right sphenoid sinus on computed tomography. The tip of the broken osteotome (Bauer) was confirmed after the intraoperative instruments were investigated. The foreign body was removed using an interventional endoscope and navigation computed tomography, and a good prognosis was obtained.
Body Mass Index Effect on Minimally Invasive Ventral Hernia Repair: A Systematic Review and Meta-analysis
Authors: Mazzola Poli de Figueiredo Sergio , Mao Rui-Min Diana , Dela Tejera Giovanna , Tastaldi Luciano , Villasante-Tezanos Alejandro , Lu Richard
Published: November 2023

Purpose:

Obesity is one of the most important risk factors for complications after ventral hernia repair (VHR), and minimally invasive (MIS) techniques are preferred in obese patients as they minimize wound complications. It is common practice to attempt weight loss to achieve a specific body mass index (BMI) goal; however, patients are often unable to reach it and fail to become surgical candidates. Therefore, we aim to perform a meta-analysis of studies comparing outcomes of obese and nonobese patients undergoing laparoscopic or robotic VHR.

Patients and Methods:

A literature search of PubMed, Scopus, and Cochrane Library databases was performed to identify studies comparing obese and nonobese patients undergoing MIS VHR. Postoperative outcomes were assessed by means of pooled analysis and meta-analysis. Statistical analysis was performed using RevMan 5.4. Heterogeneity was assessed with I
2 statistics.

Results:

A total of 6483 studies were screened and 26 were thoroughly reviewed. Eleven studies and 3199 patients were included in the meta-analysis. BMI >40 kg/m2 cutoff analysis included 5 studies and 1533 patients; no differences in hernia recurrence [odds ratios (OR): 1.64; 95% CI: 0.57-4.68; P = 0.36; I
2 = 47%), seroma, hematoma, and surgical site infection (SSI) rates were noted. BMI >35 kg/m2 cutoff analysis included 5 studies and 1403 patients; no differences in hernia recurrence (OR: 1.24; 95% CI: 0.71-2.16; P = 0.58; I
2 = 0%), seroma, hematoma, and SSI rates were noted. BMI >30 kg/m2 cutoff analysis included 4 studies and 385 patients; no differences in hernia recurrence (OR: 2.07; 95% CI: 0.5-8.54; P = 0.32; I
2 = 0%), seroma, hematoma, and SSI rates were noted.

Conclusion:

Patients with high BMI undergoing MIS VHR have similar hernia recurrence, seroma, hematoma, and SSI rates compared with patients with lower BMI. Further prospective studies with long-term follow-up and patient-reported outcomes are required to establish optimal management in obese patients undergoing VHR.
Comparison of Various Thyroidectomy Approaches: A Retrospective Cross-sectional Study
Authors: Lee Jeonghun , Kim Seong Hoon , Hong Hua
Published: November 2023

Background:

To avoid anterior neck scarring, numerous remote-access techniques to approach the thyroid gland (Remote access approach) have been described, including the transaxillary approach (TA), bilateral axillo-breast approach (BABA), and transoral robotic thyroidectomy (TORT). Popular worldwide, Remote access approachs have unique characteristics, advantages, and disadvantages. Herein, we investigated the characteristics of these distinct thyroidectomy approaches to aid surgeons in selecting the most appropriate method for patients.

Patients and Methods:

In total, 2351 cases of patients who underwent thyroidectomy between 2019 and 2021 were reviewed, including 1973, 281, 66, and 31 patients who underwent the conventional transcervical approach (TCA), TA, BABA, and TORT, respectively. Demographic characteristics, outcomes, and complications associated with these procedures were compared. The data were analyzed using the Student t test and the χ2 test. Kruskal-Wallis and Mann-Whitney U tests were used if normality was not found.

Results:

Central lymph nodes (LNs) were retrieved mostly in patients who underwent lobectomy through TORT (mean: 9.4, P < 0.001). Metastatic central LNs were found more frequently (mean: 1.9 in lobectomy, 3.7 in total thyroidectomy) in patients who underwent lobectomy through TCA and TORT than in those who underwent lobectomy through other approaches (mean: 1.4 and 2.4, respectively, P < 0.05). BABA group patients had significantly fewer central LNs retrieved than those in other groups in lobectomy and total thyroidectomy (mean: 4.8 and 6.2, respectively, P < 0.05). Stimulated thyroglobulin levels did not differ among the 4 groups. The incidence of transient vocal cord palsy was statistically higher in the BABA group (5 cases, 7.5%) than in the other groups; however, all patients recovered. No difference was found in permanent vocal cord palsy (0.4% in TCA) or hypoparathyroidism (1.3% to 3.1%) among the 4 groups. The tumor size was significantly larger in the BABA group than in the other groups, with 10.6% of the patients having tumors larger than 4 cm. Total thyroidectomy was performed more frequently in the BABA group (51.8%) than in the other groups (P = 0.005). The path of the external branch of the superior laryngeal nerve was more evident in TA, and the Cernea type was confirmed and preserved in 90.6% of TA cases.

Conclusions:

Owing to the differences in working space and direction of the surgical field, TA was advantageous for preserving the external branch of the superior laryngeal nerve, whereas BABA was effective for total thyroidectomy and excision of large goiters. TORT was beneficial for central compartment neck dissection. These characteristics should be considered when choosing the best approach to improving cosmesis, function, and recurrence.
Isolation and identification of endophytic fungi involved in the promotion of sesquiterpene accumulation in Syringa pinnatifolia
Authors: Gao Jiaqi , Lee Shiou Yih , Tai Badalahu , Chai Xingyun , Liu Juan
Published: November 2023

Background

The stem of Syringa pinnatifolia is used as traditional Mongolian medicine for the treatment of cardiopulmonary diseases, in which sesquiterpenes are regarded as the primary medicinal compounds. However, only S. pinnatifolia from natural stands is able to produce medicinal-grade stems when compared with that from cultivated stands. Despite the need to develop an effective technique to promote sesquiterpene accumulation in cultivated stands to ensure sustainable resource production, studies on the potential use of fungal endophytes as fungal elicitors were limited.

Objective

This study explored the potential of selected endophytic fungi isolated from the stems of wild and cultivated S. pinnatifolia and further examined their efficacy in promoting sesquiterpene production in S. pinnatifolia calli.

Results

Among the 11 fungal groups, Valsa sp, isolated from wild S. pinnatifolia, emerged as a promising fungal elicitor for promoting sesquiterpene accumulation in S. pinnatifolia. This conclusion is drawn from the production of a humulane-type sesquiterpene, known to be one of the most prevalent subtypes of sesquiterpenes in S. pinnatifolia. In addition, it was demonstrated that methyl jasmonate and salicylic acid displayed little effect on sesquiterpene accumulation in S. pinnatifolia.

Conclusions

The findings of this study lay a foundation for using fungal endophytes to promote sesquiterpene production in S. pinnatifolia. This contribution could subsequently advance the development of the local traditional medicine industry and aid in the protection of wild S. pinnatifolia.
Effect of Sevoflurane Anesthesia on Intraoperative Spikes, High-Frequency Oscillations, and Phase-Amplitude Coupling in MRI-Normal Hippocampus
Authors: Dahal Riju , Tamura Kentaro , Pan Dong-sheng , Sasaki Ryota , Takeshima Yasuhiro , Matsuda Ryosuke , Yamada Shuichi , Nishimura Fumihiko , Nakagawa Ichiro , Park Young-Soo , Hayashi Hironobu , Kawaguchi Masahiko , Nakase Hiroyuki
Published: November 2023

Purpose:

The purpose of this study was to determine the effect of sevoflurane anesthesia on spikes, high-frequency oscillations (HFOs), and phase-amplitude coupling using a modulation index in MRI-normal hippocampus, with the aim of evaluating the utility of intraoperative electrocorticography in identifying the epileptogenic hippocampus during sevoflurane administration.

Methods:

Eleven patients with intractable temporal lobe epilepsy with a normal hippocampus on MRI underwent extra-operative electrocorticography evaluation. Patients were assigned to the Ictal (+) or Ictal (−) group depending on whether the parahippocampal gyrus was included in the seizure onset zone. Intraoperative electrocorticography was performed under 0.5 and 1.5 minimum alveolar concentration of sevoflurane. The rates of spikes, ripples, fast ripples (FRs), ripples on spikes, FRs on spikes, and MI HFO
(3–4 Hz) were evaluated.

Results:

During the intraoperative electrocorticography procedure, sevoflurane administration was found to significantly increase the rate of spikes, ripples on spikes, fast ripples on spikes, and MI HFO
(3–4 Hz) in the Ictal (+) group (P < 0.01). By contrast, the Ictal (−) group exhibited a paradoxical increase in the rate of ripples and fast ripple (P < 0.05).

Conclusions:

Our findings indicate that the administration of sevoflurane during intraoperative electrocorticography in patients with MRI-normal hippocampus can lead to a dose-dependent enhancement of epileptic biomarkers (spikes, ripples on spikes, fast ripples on spikes, and MI (HFO 3-4)) in the epileptogenic hippocampus, while paradoxically increasing the rate of ripples and fast ripple in the nonepileptogenic hippocampus. These results have significant implications for the identification of the MRI-normal hippocampus that requires surgical intervention and preservation of the nonepileptogenic hippocampus.
Global Sensitivity Analysis of the Onset of Nasal Passage Infection by SARS-CoV-2 With Respect to Heterogeneity in Host Physiology and Host Cell-Virus Kinetic Interactions
Authors: Zhang Leyi , Cao Han , Medlin Karen , Pearson Jason , Aristotelous Andreas , Chen Alexander , Wessler Timothy , Forest M. Gregory
Published: November 2023

Throughout the COVID-19 pandemic, positive nasal swab tests have revealed dramatic population heterogeneity in viral titers spanning 6 orders-of-magnitude. Our goal here is to probe potential drivers of infection outcome sensitivity arising from (i) physiological heterogeneity between hosts and (ii) host-variant heterogeneity in the detailed kinetics of cell infection and viral replication. Toward this goal, we apply global sensitivity methods (Partial Rank Correlation Coefficient analysis and Latin Hypercube Sampling) to a physiologically faithful, stochastic, spatial model of inhaled SARS-CoV-2 exposure and infection in the human respiratory tract. We focus on the nasal passage as the primary origin of respiratory infection and site of clinical testing, and we simulate the spatial and dynamic progression of shed viral load and infected cells in the immediate 48 hours post infection. We impose immune evasion, i.e., suppressed immune protection, based on the preponderance of clinical evidence that nasal infections occur rapidly post exposure, largely independent of immune status. Global sensitivity methods provide the de-correlated outcome sensitivities to each source of within-host heterogeneity, including the dynamic progression of sensitivities at 12, 24, 36, and 48 hours post infection. The results reveal a dynamic rank-ordering of the drivers of outcome sensitivity in early infection, providing insights into the dramatic population-scale outcome diversity during the COVID-19 pandemic. While we focus on SARS-CoV-2, the model and methods are applicable to any inhaled virus in the immediate 48 hours post infection.
SUPPORT NEEDS AND ADAPTIVE BEHAVIOR SURVEYS: SERVICES PREDICTION AND RELATIONSHIP
Authors: Piccorelli Annalisa V. , Moody Eric J. , Heath David , Dahl Ethan , Root-Elledge Sandy
Published: November 2023

The Inventory for Client and Agency Planning (ICAP) and the Supports Intensity Scale (SIS) have been used to determine Medicaid eligibility for individuals with disabilities but are designed to capture different information. This project explored how these surveys relate to services received and each other. ICAP and SIS surveys were conducted on 125 [Blinded] adults with intellectual and developmental disabilities eligible for a Medicaid Waiver. Results suggest that both measures were strongly associated and could be used to predict services. However, this study suggests that the SIS and ICAP summary measures were separate constructs. Therefore, both instruments can be used to determine Medicaid eligibility, but implementers should be aware of differences in the types of constructs being captured.
Evidence for impaired hippocampal circuitry in schizophrenia and its link to memory dysfunction
Authors: Zadbood Asieh , Tang Yingying , Su Wenjun , Hu Hao , Capichioni Gillian , Yang Shuwen , Wang Junjie , Gasser Camille , Bein Oded , Hui Li , Jia Qiufang , Zhang Tianhong , Hong Yawen , Wang Jijun , Goff Donald , Davachi Lila
Published: November 2023

Pattern separation and pattern completion are opposing yet complementary components of mnemonic processing that heavily rely on the hippocampus. It has been shown that processing within the dentate gyrus (DG) subfield promotes pattern separation while operations within the CA3 subfield are important for pattern completion. Schizophrenia has been associated with anatomical and functional hippocampal abnormalities, including within the DG and CA3. We hypothesized that an impairment in hippocampal circuitry in individuals with first-episode schizophrenia leads to deficits in pattern separation (mnemonic discrimination) and pattern completion (recognition memory), that these deficits contribute to delusions, and that antipsychotic treatment improves circuit functioning. We measured behavioral and neural responses during the identification of new, repeated, and similar stimuli using high-resolution fMRI in 45 medication-free or minimally-treated patients with first-episode schizophrenia and 49 matched controls. We found recognition memory and pattern separation deficits in patients and a negative association between memory performance and the severity of delusions. Neural analyses revealed deficits in both univariate BOLD responses and multivariate patterns in the hippocampus during mnemonic discrimination in patients compared to controls. Importantly, by investigating the association between trial-level neural activity and behavior before and after treatment, we found that antipsychotics normalized DG activity during pattern separation and CA3 activity during pattern completion. Lastly, trial-level cortical responses during mnemonic discrimination predicted performance in patients at baseline, suggesting a compensatory role. This study provides new insight into the impact of schizophrenia and antipsychotic treatment on memory systems and uncovers systems-level contributions to pattern separation and pattern completion.
Association of optic disc parameters and glaucoma incidence based on automated segmentation, evidence from the UK Biobank
Authors: Zhu Pinxuan , He Shuang , Shi Danli , He Mingguang
Published: November 2023

Objective

To assess the correlation between glaucoma incidence and optic disc parameters obtained through an automated deep learning (DL) algorithm segmentation.

Methods and Analysis

We obtained eligible fundus photographs and corresponding participant data from the UK Biobank. To accurately assess the optic disc parameters and their relationship with glaucoma incidence using Cox proportional hazard regression models, we developed a DL algorithm that automatically segmented the optic disc and cup and calculated various parameters including the vertical cup-to-disc ratio (VCDR), ovality index, cup-to-disc area ratio, rim area, disc area, and disc rotation from the fundus photos. We performed two logistic regression models, with model A comprising sociodemographic and health covariates and model B including additional ophthalmic features. Receiver operating characteristic curves (ROC) and areas under the curve (AUC) were plotted and calculated for each model to evaluate their performance.

Results

A total of 44,376 subjects with fundus photos were included in our study. After a median follow-up of 10.1 years, 354 incident glaucoma were documented. Subjects with larger VCDR had a higher risk of incident glaucoma; the HR (95% CI) was 2.05 (1.57-2.66) in the multivariable-adjusted model (p<0.001). The results remain significant in the sensitivity analysis that excluded fundus photographs with “Reject” quality. After adding the optic disc parameters into the regression model A, the AUC increased by 4.2% to 78.6%.

Conclusion

The VCDR calculated by automatic optic disc segmentation model shows potential as a biomarker for evaluating the risk of glaucoma.

What is already known on this topic

Glaucoma is a worldwide leading cause of irreversible vision loss, and its early diagnosis is of great necessity.

What this study adds

Data from the UK Biobank shows the optic disc parameters and their relationship with glaucoma incidence.

We develop a DL-based algorithm for optic disc segmentation in Color fundus photos and validate its efficacy in glaucoma prediction.

How this study might affect research, practice or policy

The VCDR calculated using an automatic optic disc segmentation based on a DL model can serve as a biomarker to predict the incidence of glaucoma.
Personalized modeling of neurodegeneration determines dementia severity from EEG recordings
Authors: Amato L.G. , Vergani A. A. , Lassi M. , Fabbiani C. , Mazzeo S. , Burali R. , Nacmias B. , Sorbi S. , Mannella R. , Grippo A. , Bessi V. , Mazzoni A.
Published: November 2023

INTRODUCTION

Early identification of dementia is necessary for a timely onset of therapeutic care. However, cortical structural alterations associated with early dementia are difficult to disclose. METHODS: We developed a cortical model of dementia-related neurodegeneration accounting for slowing of local dynamics and global connectivity degradation. We collected EEG recordings at rest from subjects in healthy (HC), Subjective Cognitive Decline (SCD), and Mild Cognitive Impairment (MCI) condition. For each patient, we estimated neurodegeneration model parameters based on individual EEG recordings. RESULTS: Our model outperformed standard EEG analysis not only in discriminating between HC and MCI conditions (F1 score 0.95 vs 0.85) but also in identifying SCD patients with biological hallmarks of Alzheimer’s disease in the cerebrospinal fluid (recall 0.87 vs 0.50). DISCUSSION: Personalized neurodegeneration models could both support classification of MCI and assess the risk of progression from SCD to Alzheimer based only on economical and non-invasive EEG recording

ClinicalTrials.govIdentifier

NCT05569083
Impact of ‘EVEN FASTER’ concept to accelerate cervical cancer elimination in Norway: A model-based analysis
Authors: Portnoy Allison , Pedersen Kine , Kim Jane J. , Burger Emily A.
Published: November 2023

Background

Experts have proposed an ‘EVEN FASTER’ concept targeting age-groups maintaining circulation of human papillomavirus (HPV). We explored the effects of these proposals compared with cervical cancer (CC) screening-based interventions on age-standardized incidence rate (ASR) and CC elimination (<4 cases per 100,000 women) timing in Norway.

Methods

We used a model-based approach to evaluate alternative HPV vaccination and CC screening scenarios compared with a status-quo scenario reflecting previous vaccination and screening. For cohorts ages 25–35 years, we examined 11 vaccination scenarios that incrementally increased vaccination coverage from current cohort-specific rates. Each vaccination scenario was coupled with three alternative screening strategies that varied the frequency of HPV-based screening. Population- and cohort-level outcomes included ASR, lifetime risk of CC, and colposcopy referrals.

Results

Several vaccination strategies coupled with de-intensified screening frequencies lowered population ASR, but did not accelerate CC elimination unless incremental vaccination coverage reached ∼90% for vaccine-naïve cohorts. Alternative strategies that increased screening adherence could both accelerate elimination and improve ASR compared to status-quo.

Conclusions

An ‘EVEN FASTER’ campaign is unlikely to accelerate CC elimination but may reduce population-level ASR. Alternatively, targeting under- and never-screeners may both eliminate CC faster and lead to greater health benefits compared with vaccination-based interventions.
Cost-effectiveness of broadly neutralizing antibodies for infant HIV prophylaxis in settings with high HIV burdens: a simulation modeling study
Authors: Alba Christopher , Malhotra Shelly , Horsfall Stephanie , Barnhart Matthew E. , Bekker Adrie , Chapman Katerina , Cunningham Coleen K. , Fast Patricia E. , Fouda Genevieve G. , Freedberg Kenneth A. , Goga Ameena , Ghazaryan Lusine R. , Leroy Valériane , Mann Carlyn , McCluskey Margaret M. , McFarland Elizabeth J. , Muturi-Kioi Vincent , Permar Sallie R. , Shapiro Roger , Sok Devin , Stranix-Chibanda Lynda , Weinstein Milton C. , Ciaranello Andrea L. , Dugdale Caitlin M.
Published: November 2023

Introduction

Approximately 130 000 infants acquire HIV annually despite global maternal antiretroviral therapy scale-up. We evaluated the potential clinical impact and cost-effectiveness of offering long-acting, anti-HIV broadly neutralizing antibody (bNAb) prophylaxis to infants in three distinct settings.

Methods

We simulated infants in Côte d’Ivoire, South Africa, and Zimbabwe using the Cost-Effectiveness of Preventing AIDS Complications-Pediatric (CEPAC-P) model. We modeled strategies offering a three-bNAb combination in addition to WHO-recommended standard-of-care oral prophylaxis to infants: a) with known, WHO-defined high-risk HIV exposure at birth (HR-HIVE); b) with known HIV exposure at birth (HIVE); or c) with or without known HIV exposure (ALL). Modeled infants received1-dose,2-doses, orExtended(every 3 months through 18 months) bNAb dosing. Base case model inputs included 70% bNAb efficacy (sensitivity analysis range: 10-100%), 3-month efficacy duration/dosing interval (1-6 months), and $20/dose cost ($5-$100/dose). Outcomes included pediatric HIV infections, life expectancy, lifetime HIV-related costs, and incremental cost-effectiveness ratios (ICERs, in US$/year-of-life-saved [YLS], assuming a<50% GDP per capita cost-effectiveness threshold).

Results

The base case model projects that bNAb strategies targetingHIVEandALLinfants would prevent 7-26% and 10-42% additional pediatric HIV infections, respectively, compared to standard-of-care alone, ranging by dosing approach.HIVE-Extendedwould be cost-effective (cost-saving compared to standard-of-care) in Côte d’Ivoire and Zimbabwe;ALL-Extendedwould be cost-effective in South Africa (ICER: $882/YLS). BNAb strategies targetingHR-HIVEinfants would result in greater lifetime costs and smaller life expectancy gains thanHIVE-Extended. Throughout most bNAb efficacies and costs evaluated in sensitivity analyses, targetingHIVEinfants would be cost-effective in Côte d’Ivoire and Zimbabwe, and targetingALLinfants would be cost-effective in South Africa.

Discussion

Adding long-acting bNAbs to current standard-of-care prophylaxis would be cost-effective, assuming plausible efficacies and costs. The cost-effective target population would vary by setting, largely driven by maternal antenatal HIV prevalence and postpartum incidence.
Compare SGLT2I versus non-SGLT2I users in type-2 diabetic mellitus patients on GLP-1 receptor agonist: A population-based and machine learning causal inference analysis
Authors: Luo Zhiyao , Chou Oscar Hou-In , Ng Zita Man Wai , Chung Cheuk To Skylar , Chan Jeffrey Shi Kai , Chan Raymond Ngai Chiu , Lu Lei , Zhu Tingting , Cheung Bernard Man Yung , Liu Tong , Tse Gary , Zhou Jiandong
Published: November 2023

Background

Both sodium-glucose cotransporter-2 (SGLT2) inhibitors and GLP-1 receptor agonists (GLP1a) demonstrated benefits against cardiovascular diseases in type 2 diabetes (T2D). However, the effects of SGLT2I amongst patients already on GLP1a users remain unknown.

Objective

This real-world study compared the risks of cardiovascular diseases with and without exposure to SGLT2I amongst GLP1a users.

Methods

This was a retrospective population-based cohort study of patients with type-2 diabetes mellitus (T2DM) on GLP1a between 1st January 2015 and 31st December 2020 using a territory-wide registry from Hong Kong. The primary outcomes were new-onset myocardial infarction, atrial fibrillation, heart failure, and stroke/transient ischaemic attack (TIA). The secondary outcome was all-cause mortality. Propensity score matching (1:2 ratio) using the nearest neighbour search was performed. Multivariable Cox regression was used to identify significant associations. The machine learning causal inference analysis was used to estimate the treatment effect.

Results

This cohort included 2526 T2DM patients on GLP1a (median age: 52.5 years old [SD: 10.9]; 57.34 % males). The SGLT2I users and non-SGLT2I users consisted of 1968 patients and 558 patients, respectively. After matching, non-SGLT2I users were associated with high risks of myocardial infarction (Hazard ratio [HR]: 2.91; 95% Confidence Interval [CI]: 1.30-6.59) and heart failure (HR: 2.49; 95% CI: 1.22-5.08) compared to non-SGLT2I users after adjusting for demographics, comorbidities, medications, renal function, and glycaemic tests. However, non-SGLT2I users were not associated with the risks of atrial fibrillation (HR: 1.52; 95% CI: 0.65-3.53) and stroke/TIA (HR: 1.72; 95% CI: 0.70-4.24). The results remained consistent in the competing risk and the sensitivity analyses.

Conclusions

SGLT2I non-users was associated with higher risks of myocardial infarction and heart failure when compared to SGLT2I users after adjustments amongst T2DM patients on GLP1a. The result remained consistent in the machine learning causal inference analysis.

Graphical abstract
Genomic insights into the evolution of secondary metabolism ofEscovopsisand its allies, specialized fungal symbionts of fungus-farming ants
Authors: Berasategui Aileen , Salem Hassan , Moller Abraham G. , Christopher Yuliana , Vidaurre-Montoya Quimi , Conn Caitlin , Read Timothy D. , Rodrigues Andre , Ziemert Nadine , Gerardo Nicole
Published: November 2023

The metabolic intimacy of symbiosis often demands the work of specialists. Natural products and defensive secondary metabolites can drive specificity by ensuring infection and propagation across host generations. But in contrast to bacteria, little is known about the diversity and distribution of natural product biosynthetic pathways among fungi and how they evolve to facilitate symbiosis and adaptation to their host environment. In this study, we define the secondary metabolism ofEscovopsisand closely related genera, members of which are specialized, diverse ascomycete fungi best known as mycoparasites of the fungal cultivars grown by fungus-growing ants. We ask how the gain and loss of various biosynthetic pathways corresponds to divergent lifestyles. Long-read sequencing allowed us to define the chromosomal features of representativeEscovopsisstrains, revealing highly reduced genomes (21.4-38.3 Mb) composed of 7-8 chromosomes.Escovopsisgenomes are highly co-linear, with genes localizing not only in the same chromosome, but also in the same order. Macrosynteny is high withinEscovopsisclades, and decreases with increasing phylogenetic distance, while maintaining a high degree of mesosynteny. To explore the evolutionary history of biosynthetic pathways in this group of symbionts relative to their encoding lineages, we performed an ancestral state reconstruction analysis, which revealed that, while many secondary metabolites are shared with non-ant associated sordariomycetes, 56 pathways are unique to the symbiotic genera. Reflecting adaptation to diverging ant agricultural systems, we observe that the stepwise acquisition of these pathways mirrors the ecological radiations of attine ants and the dynamic recruitment and replacement of their fungal cultivars. As different clades encode characteristic combinations of biosynthetic gene clusters, these delineating profiles provide important insights into the possible mechanisms underlying specificity between these symbionts and their hosts. Collectively, our findings shed light on the evolutionary dynamic nature of secondary metabolism inEscovopsisand its allies, reflecting adaptation of the symbionts to an ancient agricultural system.