bluuebunny/crossref_metadata_2025 huggingface dataset:
Tryptophan–Kynurenine Pathway Activation and Cognition in Virally Suppressed Women With HIV
Authors: Shorer Eran Frank , Dastgheyb Raha M. , French Audrey L. , Daubert Elizabeth , Morack Ralph , Yohannes Tsion , Clish Clary , Gustafson Deborah , Sharma Anjali , Rogando Andre , Qi Qibin , Burgess Helen , Rubin Leah H. , Weber Kathleen M.
Published: May 2024

Background:

Immune and cognitive dysfunction persists even in virally suppressed women with HIV (VS-WWH). Since inflammation and HIV proteins induce the enzyme indoleamine 2,3-dioxygenase (IDO), converting tryptophan (T) to kynurenine (K) while producing downstream neurotoxic metabolites, we investigated IDO activation (KT ratio) in relation to cognition in VS-WWH and demographically similar women without HIV (WWoH).

Methods:

Ninety-nine VS-WWH on stable antiretroviral therapy and 102 WWoH (median age 52 vs 54 years; 73% vs 74% Black, respectively) from the New York and Chicago sites of the Women's Interagency HIV Study (WIHS) completed a neuropsychological test battery assessing motor function, processing speed, attention/working memory, verbal fluency, verbal learning and memory, and executive function and had plasma measured for tryptophan–kynurenine metabolites through liquid chromatography-tandem mass spectrometry and monocyte-derived [soluble cluster of differentiation-14 (sCD14), soluble cluster of differentiation-163 (sCD163), monocyte chemoattractant protein-1 (MCP-1)] plus general inflammatory markers [tumor necrosis factor alpha-2 receptor (TNF-R2), high-sensitivity C-reactive protein, high-sensitivity interleukin-6] through enzyme-linked immunosorbent assays between 2017 and 2020.

Results:

VS-WWH had a higher KT ratio (P < 0.01) and higher sCD14 levels (P < 0.05) compared with WWoH. Higher sCD163 was associated with higher KT ratio (R = 0.29, P < 0.01) and worse fine motor function in VS-WWH; after adjusting for sCD163 and sCD14 in multivariable regressions, higher KT ratio remained significantly associated with impaired fine motor function in VS-WWH only (standardized β = −0.29, P < 0.05). IDO activation was not associated with cognition in WWoH.

Conclusions:

IDO activation (K:T) was associated with worse fine motor control in VS-WWH independent of measured systemic inflammation. Further studies investigating biological mechanisms linking IDO activation to fine motor function among VS-WWH are warranted.
Effectiveness of Using Additional HIV Self-Test Kits as an Incentive to Increase HIV Testing Within Assisted Partner Services
Authors: Roy Paladhi Unmesha , Katz David A. , Otieno George , Hughes James P. , Thirumurthy Harsha , Lagat Harison , Masyuko Sarah , Sharma Monisha , Macharia Paul , Bosire Rose , Mugambi Mary , Kariithi Edward , Farquhar Carey
Published: May 2024

Background:

Incentives have shown mixed results in increasing HIV testing rates in low-resource settings. We investigated the effectiveness of offering additional self-tests (HIVSTs) as an incentive to increase testing among partners receiving assisted partner services (APS).

Setting:

Western Kenya.

Methods:

We conducted a single-crossover study nested within a cluster-randomized controlled trial. Twenty-four facilities were randomized 1:1 to (1) control: provider-delivered testing or (2) intervention: offered 1 HIVST or provider-delivered testing for 6 months (pre-implementation), then switched to offering 2 HIVSTs for 6 months (post-implementation). A difference-in-differences approach using generalized linear mixed models, accounting for facility clustering and adjusting for age, sex, and income, was used to estimate the effect of the incentive on HIV testing and first-time testing among partners in APS.

Results:

March 2021-June 2022, 1127 index clients received APS and named 8155 partners, among whom 2333 reported a prior HIV diagnosis and were excluded from analyses, resulting in 5822 remaining partners: 3646 (62.6%) and 2176 (37.4%) in the pre-implementation and post-implementation periods, respectively. Overall, 944/2176 partners (43%) were offered a second HIVST during post-preimplementation, of whom 34.3% picked up 2 kits, of whom 71.7% reported that the second kit encouraged HIV testing. Comparing partners offered 1 vs. two HIVSTs showed no difference in HIV testing (relative risk: 1.01, 95% confidence interval: 0.951 to 1.07) or HIV testing for the first time (relative risk: 1.23, 95% confidence interval: 0.671 to 2.24).

Conclusions:

Offering a second HIVST as an incentive within APS did not significantly impact HIV testing or first-time testing, although those opting for 2 kits reported it incentivized them to test.
Cranial Nerve Injuries in Orthognathic Surgery
Authors: Fukuyama Sotatsu , Lo Lun-Jou
Published: May 2024

Orthognathic surgery is increasingly utilized to correct facial deformities and dental malocclusions, as well as to enhance facial aesthetics. Significant advancements in surgical planning and execution have made it more widespread and accessible. However, unfavorable outcomes or complications can occur, leading to potentially severe and possibly long-term consequences, such as cranial nerve injuries. This literature review investigates the cranial nerve complications associated with orthognathic surgery. We conducted an extensive search across available databases, analyzing relevant studies published up to September 30, 2023. Two authors independently selected articles for full-text review based on their titles and abstracts. The eligible studies reported cranial nerve injuries in individuals who had undergone orthognathic surgery. Our findings highlight the risk of cranial nerve injuries, their possible mechanism, management, and outcomes. It is imperative for surgeons to remain vigilant and informed and to communicate such information during preoperative patient consultation.
Photographic Parameters in Three-Dimensional Facial Image Acquisition. A Scoping Review
Authors: Muñoz Gonzalo , Brito Leonardo , Olate Sergio
Published: May 2024

Objective:

Orthognathic surgery is a viable and reproducible treatment for facial deformities. Despite the precision of the skeletal planning of surgical procedures, there is little information about the relations between hard and soft tissues in three-dimensional (3D) analysis, resulting in unpredictable soft tissue outcomes. Three-dimensional photography is a viable tool for soft tissue analysis because it is easy to use, has wide availability, low cost, and is harmless. This review aims to establish parameters for acquiring consistent and reproducible 3D facial images.

Methods:

A scoping review was conducted across PubMed, SCOPUS, Scientific Electronic Library Online (SciELO), and Web of Science databases, adhering to “Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews” guidelines. Articles presenting 3D facial photographs in the diagnostic phase were considered.

Results:

A total of 79 articles were identified, of which 29 were selected for analysis.

Conclusion:

The predominant use of automated systems like 3dMD and VECTRA M3 was noted. User positioning has highest agreement among authors. Noteworthy aspects include the importance of proper lighting, facial expression, and dental positioning, with observed discrepancies and inconsistencies among authors. Finally, the authors proposed a 3D image acquisition protocol based on this research findings.
Assessing the Current State of Microtia Reconstruction in the United States
Authors: Reddy Narainsai K. , Shah Nikhil D. , Alias Basil P. , Allison Sophia , Chwa Emily S. , Yamada Akira
Published: May 2024

Objective:

Microtia is a congenital ear deformity with variability in surgical techniques and tools across surgeons pursuing an autologous reconstruction. Different techniques have emerged over time, and surgeons opt for various tools to aid in creating the complex three-dimensional cartilaginous ear framework. The purpose of this study was to understand the current state of microtia reconstruction in the United States.

Methods:

Microtia surgeons affiliated with the nonprofit, Ear Community, were invited to complete a 20-item survey. Data were collected on demographic information regarding surgeons, considerations when approaching microtia repair in patients, and techniques and comfort levels. Additional data were collected on materials, tools, flaps, and skin grafts used for reconstruction.

Results:

Twenty-two surgeons responded to the survey reporting 3 different techniques learned and utilized in practice including the Brent, Nagata, and Firmin techniques. About two-thirds of surgeons were “extremely comfortable” with their techniques and one-third were “extremely uncomfortable” or “somewhat uncomfortable.” Most respondents reported using a tunneled temporoparietal fascial flap or a posterior fascial flap along with a full-thickness skin graft for the second stage (ear elevation). Most surgeons utilized a combination of scalpels and gouges when carving the ear framework along with sutures or wire.

Conclusions:

This study highlights the current state of autogenous microtia reconstruction underscoring the variability in approaches and preferences. These data may guide future directions that aim to improve patient outcomes. Surgeons may gain insight into different practices and choose to adopt different aspects to enhance their surgical approach.
Anatomic Study of Vascular Supply of the External Ear Using CT Angiography in Congenital Microtia
Authors: Gong Zhicheng , Cao Liexu , Huang Kun , Xiao Leqiang , Huang Jinjun
Published: May 2024

Background:

The morphology of the arteries of the external ear on the affected side of congenital microtia differs from normal. The present study aimed to use computed tomography angiography (CTA) to describe the anatomic variations of arteries in microtia and provide theoretical guidance for the first stage of autologous auricular reconstruction by the 2-stage method.

Methods:

Ten patients with unilateral microtia from May 2021 to August 2021 were included. Computed tomography angiography and 3-dimensional reconstruction were used to analyze the supply and branches of the main arteries of the auricle. The number of the superficial temporal artery (STA) and posterior auricular artery (PAA) branches to the auricle, vessel diameter, and the presence or absence of the STA and PAA branches were documented. The skin flap and incision were designed combined with the anatomic of auricular arteries.

Results:

The blood supply of the auricle mainly came from the STA and PAA. The STA’s preauricular branch and PAA’s posterior auricular branch were absent to varying degrees, and the middle branch was more prominent. The average diameter of the STA on the healthy auricle was 3.07±0.96 mm, and the average diameter of the PAA was 1.72±0.50 mm. The average diameter of the STA on the microtia auricle was 2.65±0.42 mm, and the average diameter of the PAA was 1.53±0.67 mm. There was a statistically significant difference in the diameter of STA between the healthy auricle and the microtia auricle (P=0.006). However, there was no significant difference in the diameter of the PAA between the healthy auricle and the microtia auricle (P=0.112). The skin flap and incision were designed and combined with the preoperative CTA images, and no flap necrosis was observed in all patients.

Conclusion:

The vascular distribution of arteries in microtia patients was clearly and accurately assessed by CTA. In our experience, the data and detailed imaging were useful in designing skin flaps and incisions during the first stage of autologous auricular reconstruction by the 2-stage method.
Bioinformatics Analysis of Hub Genes in Craniofacial Microsomia Combined With Congenital Heart Disease
Authors: Li Zhifeng , Sun Zhenzhen , Zhao Shanbaga , Zang Tianying , Zhang Zhiyong , Tang Xiaojun
Published: May 2024

Objective:

The primary objective of this study was to investigate potential mechanisms and explore hub genes of craniofacial microsomia (CFM) patients associated with congenital heart defects (CHD).

Methods:

Initially, the authors acquired target gene data related to CFM and congenital cardiac anomalies. Subsequently, the authors established a protein-protein interaction (PPI) network. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses and molecular complex detection were conducted using Metascape. Finally, the authors hub genes were screened by the cytoHubba plugin.

Results:

A total of 43 CFM genes and 120 optimal CHD candidate genes were selected. The PPI networks for pathogenic genes contained 163 nodes and 1179 edges. Functional enrichment analysis largely focused on tissue formation and development. Five modules were identified from the PPI network, and 7 hub genes were screened out. The genes most relevant to CFM associated with congenital cardiac anomalies pathogenesis included fibroblast growth factor 3, GATA binding protein 3, nuclear factor of activated T cells 1, histone cell cycle regulator, EPAS1, mitogen-activated protein kinase 1, and CRK like proto-oncogene, adaptor protein.

Conclusions:

This study identified some significant hub genes, pathways, and modules of CFM associated with CHD by bioinformatics analyses. Our findings indicate that gene subfamilies fibroblast growth factor 3, GATA binding protein 3, nuclear factor of activated T cells 1, histone cell cycle regulator, EPAS1, mitogen-activated protein kinase 1, and CRK like proto-oncogene, adaptor protein may have had significant involvement in both CFM and CHD.
Basic and Informative Photographic Standards for Cleft Lip Patients
Authors: Chen Xinxin , Wang Zhiyan , Song Tao
Published: May 2024

Background:

Standardized and reliable medical photographs are crucial for preoperative and postoperative comparisons and academic communication in the medical field. There is limited research on photographic techniques in patients with cleft lip. Deformities of the lip and nose in patients with cleft lip are not only associated with morphological abnormalities but also with abnormalities of muscle function.

Methods:

Considering the morphology and function of the lips and nose in cleft lip patients, the study captured the deformity of cleft lip patients in 6 positions: frontal view, 45 degrees left-right tilted side view, 90 degrees left-right tilted side view, and basal view, and in 5 facial expressions: tightly closed lips, slightly open mouth, smiling, teeth bared, and pout.

Results:

In 6 different positions and 5 different expressions, we took pictures of lip and nasal deformities covering most of the common deformities in patients with cleft lip, such as white lip scarring, interruption of continuity of vermillion border, lip prolapse, asymmetric corners of the mouth, collapsed ala nasi, loss of the nasal base and deviated nasal septum.

Conclusions:

This paper suggests a set of effective, easy-to-follow, and precise photographic protocols to assist cleft lip surgeons in capturing suitable and informative, high-quality 2D digital photographs.

Level of Evidence:

Level—V.
Pediatric Facial Fractures: Demographics, Injury Patterns, and Associated Injuries in 3334 Patients
Authors: Irgebay Zhazira , Glenney Anne E. , Beiriger Justin W. , Smetona John , Dixon Angel’Niqua , Kass Nicolás M. , Mocharnuk Joseph W. , Anstadt Erin , Dvoracek Lucas A. , Saladino Richard A. , Losee Joseph E. , Goldstein Jesse A.
Published: May 2024

Pediatric craniofacial fractures are fundamentally distinct from their adult counterparts because of unique injury patterns and effects on future growth. Understanding patterns and injury context informs management and risk mitigation. Previous studies include only inpatients, operative patients, or are specialty-specific. In contrast, our study presents a comprehensive assessment of all pediatric facial fracture patients seen at a single institution. Patients under 18 years old who were evaluated for facial fractures at a level I pediatric trauma center between 2006 and 2021 were reviewed. Subanalysis was performed for groups defined by age. Variables studied included demographics, etiology, fracture pattern, associated injuries, management, and outcomes. Three thousand thirty-four patients were included. Mean age at presentation was 11.5 to 4.9 years. The majority were Caucasian (82.6%) and male (68.4%). Sports were the leading cause of injury in older patients (42.2% of patients over 12 y), compared with activities of daily living in patients under 6 years (45.5%). Thirty-two percent of patients were hospitalized, 6.0% required ICU care, and 48.4% required surgery. Frequency of ICU admission decreased with age (P<0.001), whereas operative intervention increased with age (P<0.001). Zygomaticomaxillary complex (P=0.002) and nasal fractures (P<0.001) were common in older patients, whereas younger patients experienced more skull (P<0.001) and orbital fractures (P<0.001). The most associated injuries were soft tissue (55.7%) and neurologic (23.6%). This large-scale study provides updated characterization of craniofacial fractures in the pediatric population, providing a necessary framework for future studies on outcomes assessments and preventative care.
The Effects of a Cool Saline Solution Irrigation on Mandibular Third Molar Extraction Site: A Postoperative Split-Mouth Evaluation
Authors: Ronsivalle Vincenzo , Cicciù Marco , Fiorillo Luca
Published: May 2024

Objective:

This study aimed to evaluate the effects of sterile saline solution irrigation (lavage) performed after mandibular third molar extraction on postoperative complications, utilizing a split-mouth randomized clinical trial design.

Methods:

Seventeen healthy participants requiring bilateral mandibular third molar extraction were enrolled in this single-center study. In each participant, one impacted third molar was designated as the experimental group and subjected to saline lavage at 4 °C. In contrast, the control group was the other impacted third molar, undergoing saline lavage at 25 °C. Various parameters, including postoperative pain, mouth opening, and facial swelling, were assessed using standardized measures and three-dimensional facial scanning at multiple time points.

Results:

The average age of participants was 26.66 ± 4.1 years, with no postoperative complications observed in either group. The duration of surgery did not significantly differ between groups. Postoperative pain was significantly reduced in the experimental group during the immediate postoperative period compared with the control group, but this difference diminished over time. No significant differences were observed in mouth opening or facial swelling between groups at any time.

Conclusion:

In site 4 °C, sterile saline solution irrigation after mandibular third molar extraction may effectively reduce early postoperative complications, particularly pain, without prolonging surgical duration.
Validating a New Surgical Gouge for Autogenous Ear Reconstruction During Simulated Microtia Workshops
Authors: Alias Basil P. , Reddy Narainsai K. , Shah Nikhil D. , Chwa Emily S. , Yamada Akira
Published: May 2024

Autologous ear reconstruction remains a gold standard surgical technique for the treatment of external ear deformities. This highly technical procedure requires experience, an understanding of aesthetic principles, and a surgical approach that can consistently produce optimal results. As an experienced microtia surgeon having trained under Dr Satoru Nagata, the senior author has emphasized the importance of appropriate surgical tools during this procedure. Here, we present results of a novel surgical handle and gouge meant to optimize complex cartilage carving. The senior author regularly holds microtia workshops to help train individuals around the United States. During 2 of such workshops held in 2022, participants were given access to both the standard, commercially available surgical gouge as well as a prototype of a novel surgical gouge developed by the authors. Participants were then given a Likert-scale survey to assess their subjective feedback for both tools. Twenty-seven total participants completed the postworkshop survey. Cumulatively, the results demonstrated that participants rated the custom gouge significantly higher than its counterpart (4.2 versus 3.2, P<0.001). They also had a significantly higher likelihood of using the custom gouge again (4.1 versus 3.2, P=0.023). The custom gouge designed by the senior author demonstrated higher subjective ratings when compared with what is currently available on the market. This serves as a primary validation study that demonstrates feasibility for further assessment in a true operative setting.
Prevalence and Morphometry of Occipital Foramen in Dry Skulls and its Clinical Implications
Authors: Singh Rajani
Published: May 2024

The occipital emissary foramen (OEF) located on the occipital bone transmits the occipital emissary vein, which connects the occipital vein to the confluence of cranial venous sinuses. The OEF varies in incidence, number, size, and location. Knowledge of this foramen is essential for carrying out suboccipital and transcondylar surgeries without clinical implications. Hence, the study was planned. The aim of the present study is to elaborate on incidence, location, and morphometry consisting of the number and size of this foramen in light of clinical bearing in the context of the Indian population. The study was carried out in the Department of Anatomy using 80 skulls of unknown age and sex. The occipital bone of the skull was observed for the incidence, number, size, and location of the occipital emissary vein and associated clinical implications were elaborated. The incidence of occipital foramen was 36.25% and detected in 29 skulls. All these occipital foramina were patent. The mean diameter of this foramen was 0.6 mm. The most common location of these foramina was the left side of the foramen magnum, followed by the left side of the external occipital crest. The information about the incidence, number, size, and location of OEF is important to prevent catastrophic bleeding during surgery in the region of the occipital bone. The awareness of differential morphometry and morphology of occipital foramina is of great importance for neurosurgeons during suboccipital craniotomy and skull base surgeries, including far lateral and transcondylar approaches to access posterior cranial fossa for management of pathologies in the cranial cavity.
Computed Tomography Evaluation of Frontal Sinus Volume in Migraine Patients
Authors: Elvan Özlem , Esen Kaan , Kaleağasi Şükrü Hakan , Tezer Mesut Sabri
Published: May 2024

This study aimed to assess the frontal sinus volume (FSV) on computed tomography (CT) scans in migraine patients. Cranial and paranasal CT images from 75 migraine patients (mean age: 39.14±13.63 y) and 23 control cases (mean age: 38.78±13.32 y) were analyzed retrospectively. Three-dimensionally reconstructed images of frontal sinuses were generated. Total FSV, anterolateral, and transverse diameters of the head were measured. The presence/absence and nature of supraorbital foramen and notches were evaluated. The total FSV was 8.02±5.97 cm3 in the migraine group and 8.38±4.83 cm3 in the control group, with no significant differences between them. Mean FSV values showed no statistically significant difference between females (7.79±5.85 cm3) and males (9.12±6.66 cm3) within and between the groups. Single notch was the most observed structure in both groups, with bilateral presence being the most common. Double foramen and notch were observed only in the migraine group, and the coexistence of both structures was higher in the migraine patients than in controls. There was no statistical difference in FSV between migraine and control groups, nor based on sex. Overall, the frontal region anatomy, particularly the exit locations of the supraorbital or supratrochlear foramen/notches, may be influenced by hyperplasia/hypoplasia of FSV. Therefore, assessing FSV using CT may be crucial for surgical planning in migraine patients undergoing open or endoscopic approaches to the frontal region.
Effect of Subnormothermic Machine Perfusion on the Preservation of Vascularized Composite Allografts After Prolonged Warm Ischemia
Authors: Charlès Laura , Filz von Reiterdank Irina , Lancia Hyshem H. , Shamlou Austin Alana , Berkane Yanis , Rosales Ivy , Mink van der Molen Aebele B. , Coert J.H. , Cetrulo Curtis L. , Lellouch Alexandre G. , Uygun Korkut
Published: May 2024

Background.

Warm ischemia time (WIT) and ischemia–reperfusion injury are limiting factors for vascularized composite allograft (VCA) transplantation. Subnormothermic machine perfusion (SNMP) has demonstrated the potential to extend WIT in organ transplantation. This study evaluates the effect of SNMP on VCA viability after prolonged WIT.

Methods.

Rat hindlimbs underwent WIT for 30, 45, 60, 120, 150, or 210 min, followed by 3-h SNMP. Monitoring of perfusion parameters and outflow determined the maximum WIT compatible with limb viability after SNMP. Thereafter, 2 groups were assessed: a control group with inbred transplantation (Txp) after 120 min of WIT and an experimental group that underwent WIT + SNMP + Txp. Graft appearance, blood gas, cytokine levels, and histology were assessed for 21 d.

Results.

Based on potassium levels, the limit of WIT compatible with limb viability after SNMP is 120 min. Before this limit, SNMP reduces potassium and lactate levels of WIT grafts to the same level as fresh grafts. In vivo, the control group presented 80% graft necrosis, whereas the experimental group showed no necrosis, had better healing (P = 0.0004), and reduced histological muscle injury (P = 0.012). Results of blood analysis revealed lower lactate, potassium levels, and calcium levels (P = 0.048) in the experimental group. Both groups presented an increase in interleukin (IL)-10 and IL-1b/IL-1F2 with a return to baseline after 7 to 14 d.

Conclusions.

Our study establishes the limit of WIT compatible with VCA viability and demonstrates the effectiveness of SNMP in restoring a graft after WIT ex vivo and in vivo, locally and systemically.
Identifying Population-Level and Within-Hospital Disparities in Surgical Care
Authors: de Jager Elzerie , Osman Samia Y , Sheu Christina , Moberg Esther , Ye Jamie , Liu Yaoming , Cohen Mark E , Burstin Helen R , Hoyt David B , Schoenfeld Andrew J , Haider Adil H , Ko Clifford Y , Maggard-Gibbons Melinda A , Weissman Joel S , Britt LD
Published: May 2024

BACKGROUND:

The lack of consensus on equity measurement and its incorporation into quality-assessment programs at the hospital and system levels may be a barrier to addressing disparities in surgical care. This study aimed to identify population-level and within-hospital differences in the quality of surgical care provision.

STUDY DESIGN:

The analysis included 657 NSQIP participating hospitals with more than 4 million patients (2014 to 2018). Multilevel random slope, random intercept modeling was used to examine for population-level and in-hospital disparities. Disparities in surgical care by Area Deprivation Index (ADI), race, and ethnicity were analyzed for 5 measures: all-case inpatient mortality, all-case urgent readmission, all-case postoperative surgical site infection, colectomy mortality, and spine surgery complications.

RESULTS:

Population-level disparities were identified across all measures by ADI, 2 measures for Black race (all-case readmissions and spine surgery complications), and none for Hispanic ethnicity. Disparities remained significant in the adjusted models. Before risk adjustment, in all measures examined, within-hospital disparities were detected in: 25.8% to 99.8% of hospitals for ADI, 0% to 6.1% of hospitals for Black race, and 0% to 0.8% of hospitals for Hispanic ethnicity. After risk adjustment, in all measures examined, less than 1.1% of hospitals demonstrated disparities by ADI, race, or ethnicity.

CONCLUSIONS:

After risk adjustment, very few hospitals demonstrated significant disparities in care. Disparities were more frequently detected by ADI than by race and ethnicity. The lack of substantial in-hospital disparities may be due to the use of postoperative metrics, small sample sizes, the risk adjustment methodology, and healthcare segregation. Further work should examine surgical access and healthcare segregation.
Isolation and characterization of a novel Waltera species and reclassification of Brotolimicola acetigignens Hitch et al. 2022 as Waltera acetigignens comb. nov.
Authors: Sakamoto Mitsuo , Hisatomi Atsushi , Ohkuma Moriya
Published: May 2024

Obligately anaerobic, Gram-stain-negative, wavy rods, strains 17YCFAHCo10, 18YCFAH0.3Co2 and 19YCFAH0.3Co2, were isolated from faecal samples of healthy Japanese people. The three isolates showed the highest 16S rRNA gene sequence similarity to Waltera intestinalis WCA3-601-WT-6HT (99.2–100 %) and Brotolimicola acetigignens f_CXYT (99.2–99.7 %). The 16S rRNA gene sequence analysis showed that the three isolates formed a cluster with W. intestinalis WCA3-601-WT-6HT. Strain 19YCFAH0.3Co2 formed a subcluster with the type strain of W. intestinalis and did not form a cluster with the other two isolates. B. acetigignens f_CXYT also formed a cluster with W. intestinalis WCA3-601-WT-6HT and three isolates. The digital DNA–DNA hybridization (dDDH) and average nucleotide identity (ANI) values between strain 19YCFAH0.3Co2 and W. intestinalis WCA3-601-WT-6HT were higher (72 % dDDH and 97 % ANI) than the cut-off values for species delimitation, indicating that strain 19YCFAH0.3Co2 is W. intestinalis. On the other hand, the dDDH and ANI values between strains 17YCFAHCo10 and 18YCFAH0.3Co2 and the type strain of W. intestinalis were lower (<34 % dDDH and <87 % ANI) than the cut-off values for species delimitation, indicating that these two isolates are different species from W. intestinalis. The percentage of conserved proteins and the average amino acid identity values support the assignment of the isolates to the genus Waltera. Strains 17YCFAHCo10 and 18YCFAH0.3Co2 could be distinguished from W. intestinalis by their inability to ferment melibiose and ribose and lack of activity for β-glucuronidase. In addition, the dDDH and ANI values between two strains (17YCFAHCo10 and 18YCFAH0.3Co2) and B. acetigignens f_CXYT were higher (>78 % dDDH and >97 % ANI), indicating these two strains and B. acetigignens are the same species. As the genus Waltera has priority, B. acetigignens is transferred to the genus Waltera as Waltera acetigignens comb. nov. The type strain of W. acetigignens is f_CXYT (=JCM 34988T=DSM 107528T).
Efficacy and safety of ethanolamine oleate in sclerotherapy in patients with difficult-to-resect venous malformations: A multicenter, open-label, single-arm study
Authors: Ozaki Mine , Nomura Tadashi , Osuga Keigo , Kurita Masakazu , Hayashi Ayato , Yuzuriha Shunsuke , Aramaki-Hattori Noriko , Hikosaka Makoto , Nozaki Taiki , Ozeki Michio , Ochi Junko , Akiyama Shimpei , Kakei Yasumasa , Miyakoda Keiko , Kashiwagi Naoko , Yasuda Takahiro , Iwashina Yuki , Kaneko Tsuyoshi , Kamibeppu Kiyoko , Soejima Takafumi , Harii Kiyonori
Published: May 2024

Objective

To evaluate the efficacy and safety of sclerotherapy in patients with difficult-to-resect venous malformations treated with ethanolamine oleate.

Design and setting

This investigator-initiated clinical trial employed a multicenter, single-arm, open-label design and was conducted in Japan.

Patients

Overall, 44 patients with difficult-to-resect venous malformations were categorized into two cohorts: 22 patients with cystic-type malformations and 22 patients with diffuse-type malformations.

Interventions

Patients received injections of 5% ethanolamine oleate solution, double diluted with contrast or normal saline, with a maximum dose of 0.4 mL/kg. The same method of administration was used for children (<15 years old). The maximum volume of the prepared solution in one treatment was 30 mL.

Evaluation methods

Treatment efficacy was assessed by evaluating changes in lesion volume using magnetic resonance imaging and changes in pain using a visual analog scale.

Results

Among the 45 patients who consented, one was excluded owing to potential intracranial involvement of venous malformations during screening. Regarding the primary outcome, 26 of 44 patients (59.1%, 95% confidence interval: 44.41–72.31%) achieved ≥ 20% reduction in malformation volume, with 16 patients having cystic lesions (72.7%, 51.85–86.85%) and 10 patients having diffuse lesions (45.5%, 26.92–65.34%). Both cohorts showed significant improvement in self-reported pain scores associated with lesions 3 months post-sclerotherapy. No death or serious adverse events occurred. Hemoglobinuria was observed in 23 patients (52%), a known drug-related adverse event. Prompt initiation of haptoglobin therapy led to full recovery within a month for these patients.

Conclusions

Ethanolamine oleate shows potential as a therapeutic sclerosing agent for patients with difficult-to-resect venous malformations.
Comparing Scientific Machine Learning with Population Pharmacokinetic and Classical Machine Learning Approaches for Prediction of Drug Concentrations
Authors: Valderrama Diego , Teplytska Olga , Koltermann Luca Marie , Trunz Elena , Schmulenson Eduard , Fritsch Achim , Jaehde Ulrich , Fröhlich Holger
Published: May 2024

A variety of classical machine learning (ML) approaches have been developed over the past decade aiming to individualize drug dosages based on measured plasma concentrations. However, the interpretability of these models is challenging as they do not incorporate information on pharmacokinetic (PK) drug disposition. In this work we compare drug plasma concentraton predictions of well-known population PK (PopPK) modeling with classical machine learning models and a newly proposed scientific machine learning (MMPK-SciML) framework. MMPK-SciML lets us estimate PopPK parameters and their inter-individual variability (IIV) using multimodal covariate data of each patient and does not require assumptions about the underlying covariate relationships. A dataset of 541 fluorouracil (5FU) plasma concentrations as example for an intravenously administered drug and a dataset of 302 sunitinib and its active metabolite concentrations each, as example for an orally administered drug were used for analysis. Whereas classical machine learning models were not able to describe the data sufficiently, MMPK-SciML allowed us to obtain accurate drug plasma concentration predictions for test patients. In case of 5FU, goodness-of-fit shows that the MMPK-SciML approach predicts drug plasma concentrations more accurately than PopPK models. For sunitinib, we observed slightly less accurate drug concentration predictions compared to PopPK. Overall, MMPK-SciML has shown promising results and should therefore be further investigated as a valuable alternative to classical PopPK modeling, provided there is sufficient training data.
Placental and Immune Cell DNA Methylation Reference Panel for Bulk Tissue Cell Composition Estimation in Epidemiological Studies
Authors: Campbell Kyle A. , Colacino Justin A. , Dou John , Dolinoy Dana C. , Park Sung Kyun , Loch-Caruso Rita , Padmanabhan Vasantha , Bakulski Kelly M.
Published: May 2024

To distinguish DNA methylation (DNAm) from cell proportion changes in whole placental tissue research, we developed a robust cell type-specific DNAm reference to estimate cell composition. We collated newly collected and existing cell type DNAm profiles quantified via Illumina EPIC or 450k microarrays. To estimate cell composition, we deconvoluted whole placental samples (n=36) with robust partial correlation based on the top 50 hyper- and hypomethylated sites per cell type. To test deconvolution performance, we evaluated RMSE in predicting principal component one of DNAm variation in 204 external placental samples. We analyzed DNAm profiles (n=368,435 sites) from 12 cell types: cytotrophoblasts (n=18), endothelial cells (n=19), Hofbauer cells (n=26), stromal cells (n=21), syncytiotrophoblasts (n=4), six lymphocyte types (n=36), and nucleated red blood cells (n=11). Median cell composition was consistent with placental biology: 60.4% syncytiotrophoblast, 17.1% stromal, 8.8% endothelial, 4.5% cytotrophoblast, 3.9% Hofbauer, 1.7% nucleated red blood cells, and 1.2% neutrophils. Our expanded reference outperformed an existing reference in predicting DNAm variation (15.4% variance explained, IQR=21.61) with cell composition estimates (RMSE:10.51 vs. 11.43, p-value<0.001). This cell type reference can robustly estimate cell composition from whole placental DNAm data to detect important cell types, reveal biological mechanisms, and improve casual inference.
Adaptation of pain-related projection neurons in acute but not chronic pain
Authors: Title Ben , Velasco Enrique , Engelmayer Nurit , Rayi Prudhvi Raj , Yanai Roy , Hart Shmuel , Katz Ben , Lev Shaya , Yarom Yosef , Binshtok Alexander M
Published: May 2024

Pain hypersensitivity is associated with increased activity of peripheral and central neurons along the pain neuroaxis1. On the other hand, in other neuronal systems, increased activity leads to adaptive reduction of neuronal excitability to maintain homeostasis2–4. Projection neurons (PNs) of spinal and medullary dorsal horns summate the activity of primary nociceptive and local central interneurons and convey it to higher centers5. We show that at the peak of acute inflammatory pain, PNs reduce their intrinsic excitability and, consequently, action potential firing. When pain resolves, the excitability of PNs returns to baseline. Using electrophysiological and computational approaches, we found that an increase in potassium A-current (IA) underlies the decrease in the excitability of PNs in acute pain conditions. We hypothesized that an IA-induced decrease in PNs firing may restrain the output from the dorsal horn to prevent sensitization and pain chronification. Indeed, no changes of IAin PNs were observed in chronic pain conditions, and PNs exhibit increased intrinsic excitability and firing. Our results reveal an adaptive mechanism in acute pain conditions for regulating the output from the dorsal horn network, which, if interrupted, could trigger pain chronification.
A novel critic signal in identified midbrain dopaminergic neurons of mice training in operant tasks
Authors: Matsumoto Jumpei , Oberto Virginie J. , Pompili Marco N. , Todorova Ralitsa , Papaleo Francesco , Nishijo Hisao , Venance Laurent , Vandecasteele Marie , Wiener Sidney I.
Published: May 2024

In the canonical interpretation of phasic activation of dopaminergic neurons during Pavlovian conditioning, initially cell firing is triggered by unexpected rewards. Upon learning, activation instead follows the reward-predictive conditioned stimulus. When expected rewards are withheld, firing is inhibited. Here, we recorded optogenetically identified dopaminergic neurons of ventral tegmental area (VTA) in mice training in successive operant sensory discrimination tasks. A delay was imposed between nose-poke choices and trial outcome signals (reward or punishment). While animals were still performing at sub-criterion levels in the task, firing increased after correct choices, but prior to trial outcome signals. Thus, the neurons predicted whether choices would be rewarded, despite the animals’ poor behavioral performance. Surprisingly, these neurons also fired after reward delivery, as if the rewards had been unexpected, but the cells were inhibited after punishment signals, as if the reward had been expected after all. These inconsistencies suggest extension of theoretical formulations of dopaminergic neuronal activity: it would embody multiple roles in temporal difference learning and actor-critic models. Furthermore, during chance and sub-criterion performance levels during task training, the mice performed other task strategies (e.g., alternation and spatial persistence) which did not reliably elicit rewards, again while these neurons predicted the correct choice. The reward prediction activity of these neurons could serve as critic signal for the preceding choice. These finding are consistent with the notion that multiple Bayesian belief representations must be reconciled prior to reaching criterion performance levels.
Inactivation of mitochondrial complex IV inPhyscomitrium patensreveals the essential role of respiration in coordinating plants metabolism
Authors: Vera-Vives Antoni M. , Mellon Marco , Gurrieri Libero , Westhoff Philipp , Segalla Anna , Bizzotto Edoardo , Campanaro Stefano , Sparla Francesca , Weber Andreas P.M. , Alboresi Alessandro , Morosinotto Tomas
Published: May 2024

Photosynthetic organisms use sunlight as energy source but rely on respiration during the night and in non-photosynthetic tissues. Respiration is also active in photosynthetically active cells, where its role is still unclear due to a lack of viable mutants.

Plants lacking cytochrome c oxidase (complex IV) activity are generally lethal but were here isolated exploiting the possibility of generating knockout lines through vegetative propagation in the mossPhyscomitrium patens.

The mutants showed severely impaired growth, with an altered composition of the respiratory apparatus and increased electron transfer through the alternative oxidase. The light phase of photosynthesis remained largely unaffected while the efficiency of carbon fixation was moderately reduced. Transcriptomic and metabolomic analyses showed that the disruption of the cytochrome pathway had broad consequences for carbon and nitrogen metabolism. A major alteration in nitrogen assimilation was observed with a general reduction in amino acid abundance. A partial rescue of the growth could be obtained by growing the plants with an external supply of amino acids but not with sugars, demonstrating that respiration in plant photosynthetic cells plays an essential role at the interface between carbon and nitrogen metabolism and a key role in providing carbon skeletons for amino acid biosynthesis.
Quick, Don’t Move!: Wh-Movement and Wh-In-Situ Structures in Rapid Parallel Reading – EEG studies in English, Urdu, and Mandarin Chinese
Authors: Chacón Dustin A. , Dunagan Donald , McLendon Jill , Khokhar Hareem , Hoque Zahin
Published: May 2024

A fundamental question in the cognitive neuroscience of language is how grammatical representations are reflected in the organization and activity of the brain. This is challenging in part because superficial differences between languages, e.g., word order, exert different demands on the memory systems that process these structures. Here, we present an electroencephalography (EEG) study to investigate the brain’s responses towh-constructions in English, Urdu, and Mandarin Chinese. In addition to the different word orders, writing systems, and morphological typologies of the 3 languages, these languages diverge with regard to howwh-constructions are formed: English requires filler-gap dependencies forwh-objects, whereas Urdu and Mandarin Chinese do not. We use a rapid parallel reading task, in which short sentences are displayed in parallel for 200ms to mitigate the different demands placed on memory systems. We show that neural responses distinguishwh-object constructions from their controls in midline anterior (Urdu, Mandarin Chinese) and right posterior sensors (English, Mandarin Chinese), from 200–400ms (English, Mandarin Chinese) and 500–800ms (English, Urdu). Although there is no detectable uniform, language-invariant response towh-constructions across languages, there are a number of shared features in the evoked response between any pair of languages, i.e.,wh-in-situconstructions generate an evoked response in midline anterior sensors. Moreover, behavioral evidence shows a robust cross-language cost of processingwh-object constructions, regardless of their surface form. This demonstrates that readers of diverse languages can process some grammatical information in a short 200ms fixation, and that the RPVP methodology may enable new ways of linking cognitive neuroscience of language to comparative syntax, i.e., the systematic description of similarities and differences between grammatical structures.
Mitochondrial DNA removal is essential for sperm development and activity
Authors: Chen Zhe , Zhang Fan , Lee Annie , Yamine Michaela , Wang Zong-Heng , Zhang Guofeng , Combs Chris , Xu Hong
Published: May 2024

During multicellular organisms’ reproduction, organelles, cytoplasmic materials, and mitochondrial DNA (mtDNA) are all derived from maternal lineage. Active mtDNA elimination during spermatogenesis has emerged as a conserved mechanism ensuring the uniparental mitochondrial inheritance in animals1 2 3 4. However, given the existence of post-fertilization processes degrading sperm mitochondria5 6 7 8 9, the physiological significance of sperm mtDNA removal is not clear. We report that mtDNA removal is indispensable for sperm development and activity. We uncover a novel mitochondrial exonuclease, ExoA (Exonuclease A) that is specially expressed in late spermatogenesis and exclusively required for mtDNA elimination. Loss of ExoA impairs mtDNA clearance in elongated spermatids and impedes the progression of individualization complexes that strip away cytoplasmic materials and organelles. Additionally, persistent mtDNA in mature sperm causes marked fragmentation of nuclear genome and complete sterility ofexoAmutant male flies. All these defects can be suppressed by expressing a mitochondrially targeted bacterial exonuclease to ectopically remove mtDNA. Our work illustrates the developmental necessity of mtDNA clearance for the effective cytoplasm removal at the end of spermatid morphogenesis and to prevent potential nuclear-mito imbalance in mature sperms, in which the activity of nuclear genome is shutdown. Hence, the uniparental mitochondrial inheritance seems co-evolved with a key feature of sexual reproduction, the asymmetry between two gametes.
Chronic fluoxetine treatment desensitizes serotoninergic inhibition of GABA inputs and the intrinsic excitability of dorsal raphe serotonin neurons
Authors: Zhang Wei , Jin Ying , Zhou Fu-Ming
Published: May 2024

Dorsal raphe serotonin (5-hydroxytryptamine, 5-HT) neurons are spontaneously active and release 5-HT that is critical to normal brain function such mood and emotion. Serotonin reuptake inhibitors (SSRIs) increase the synaptic and extracellular 5-HT level and are effective in treating depression. Treatment of two weeks or longer is often required for SSRIs to exert clinical benefits. The cellular mechanism underlying this delay was not fully understood. Here we show that the GABAergic inputs inhibit the spike firing of raphe 5-HT neurons; this GABAergic regulation was reduced by 5-HT, which was prevented by G-protein-activated inwardly rectifying potassium (Girk) channel inhibitor tertiapin-Q, indicating a contribution of 5-HT activation of Girk channels in GABAergic presynaptic axon terminals. Equally important, after 14 days of treatment of fluoxetine, a widely used SSRI type antidepressant, this 5-HT inhibition of GABAergic inputs was substantially downregulated. Furthermore, the chronic fluoxetine treatment substantially downregulated the 5-HT activation of the inhibitory Girk current in 5-HT neurons. Taken together, our results suggest that chronic fluoxetine administration, by blocking 5-HT reuptake and hence increasing the extracellular 5-HT level, can downregulate the function of 5-HT1B receptors on the GABAergic afferent axon terminals synapsing onto 5-HT neurons, allowing extrinsic, behaviorally important GABA neurons to more effectively influence 5-HT neurons; simultaneously, chronic fluoxetine treatment also downregulate somatic 5-HT autoreceptor-activated Girk channel-mediated hyperpolarization and decrease in input resistance and intrinsic excitability, rendering 5-HT neurons resistant to autoinhibition and leading to increased 5-HT neuron activity, potentially contributing to the antidepressant effect of SSRIs.