bluuebunny/crossref_metadata_2025 huggingface dataset:
Association of depression and suicidal behaviour reporting with HIV integrase inhibitors: a global pharmacovigilance study
Authors: Préta Laure-Hélène , Chroboczek Tomasz , Treluyer Jean-Marc , Chouchana Laurent
Published: June 2023

Objectives

Concerns have been raised regarding neuropsychiatric adverse drug reactions of integrase inhibitors (INSTIs) in patients living with HIV. The aim of this study was to assess the risk of depression and suicidality reporting with INSTIs based on a global pharmacovigilance database.

Methods

Depression and suicidality cases in patients treated with INSTIs were identified within the WHO global database of individual case safety reports, VigiBase. Risk of depression and suicidality reporting with INSTIs compared with other ART was assessed using disproportionality analyses (case/non-case statistical approach).

Results

Of 19 991 410 reports over the study period, 124 184 reports concerned patients exposed to ART, including 22 661 patients exposed to an INSTI. Among patients treated with an INSTI, 547 cases of depression and 357 cases of suicidality were identified. Disproportionality analyses showed that depression [reporting OR (ROR) 3.6; 95% CI: 3.2–4.0] and suicidality (ROR 4.7; 95% CI: 4.1–5.4) were more reported with the use of INSTIs compared with other ART. Amongst INSTIs, depression reporting was significantly greater for bictegravir and dolutegravir, whereas suicidality reporting was significantly greater for dolutegravir only.

Conclusions

Our findings suggest that depression and suicidality are adverse drug reactions of all INSTI agents, especially dolutegravir, which may occur within the first months of therapy.
Psychosocial interventions for personality and behavior changes in adults with a brain tumor: A scoping review
Authors: McDougall Emma , Breen Lauren J , Nowak Anna K , Dhillon Haryana M , Halkett Georgia K B
Published: June 2023

Background

The objective of this scoping review was to describe the intervention characteristics and effectiveness of psychosocial interventions aimed at managing personality and behavior changes in people with brain tumors. A secondary objective was to explore if these interventions had an impact on outcomes for carers. Personality and behavior changes considered included aggression, apathy, paranoia, disinhibition, and emotional lability.

Methods

This review was conducted following the Joanna Briggs Institute methodology for scoping reviews and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) extension for scoping reviews. Searches were conducted in PsycINFO, CINAHL, Medline (Ovid), and Scopus. We synthesized studies published from 1996 to 2022 that evaluated interventions to manage brain tumor related personality and behavioral changes in adults. A data extraction tool were used based on the Joanna Briggs Institute template. Results are presented in a summary table and a narrative synthesis was conducted.

Results

Three thousand and five hundred and ninety-four records were screened. Title and abstract screening resulted in 29 potentially eligible studies. Full screening excluded 24 articles and 5 interventions met the inclusion criteria. The interventions were diverse in duration, delivery modality, setting, and participation (eg, the patient individually or patient and carer). The interventions reported improvements in the targeted personality and behavior change symptoms for patients with primary brain tumors. Four studies included a measure of personality and behavior change symptoms and two studies included a measure of outcomes for carers and reported improvements in carer knowledge and a reduction in carer distress. All studies sampled fewer than 100 participants. Studies had limited follow-up data and different tools were used to assess the presence and nature of personality and behavior changes.

Conclusions

There is a dearth of psychosocial interventions to support patients and their carers to manage brain tumor related personality and behavior changes.
Prevention of COVID-19 Following a Single Intramuscular Administration of Adintrevimab: Results From a Phase 2/3 Randomized, Double-Blind, Placebo-Controlled Trial (EVADE)
Authors: Ison Michael G , Weinstein Debra F , Dobryanska Marta , Holmes Anna , Phelan Anne-Marie , Li Yong , Gupta Deepali , Narayan Kristin , Tosh Kazima , Hershberger Ellie , Connolly Lynn E , Yalcin Ilker , Campanaro Ed , Hawn Pamela , Schmidt Pete ,   for the EVADE Study Group
Published: June 2023

Background

The prevention of coronavirus disease 2019 (COVID-19) in vulnerable populations is a global health priority. EVADE was a phase 2/3 multicenter, double-blind, randomized, placebo-controlled trial of adintrevimab, an extended–half-life monoclonal antibody, for postexposure (PEP) and pre-exposure prophylaxis (PrEP) of symptomatic COVID-19.

Methods

Eligible participants (vaccine-naive, aged ≥12 years) were randomized 1:1 to receive a single 300-mg intramuscular injection of adintrevimab or placebo. Primary efficacy end points were reverse transcription polymerase chain reaction (RT-PCR)–confirmed symptomatic COVID-19 through day 28 in the PEP cohort (RT-PCR-negative at baseline) and through month 3 in the PrEP cohort (RT-PCR-negative and seronegative at baseline) among participants randomized before emergence of the severe acute respiratory syndrome coronavirus 2 Omicron variant (November 30, 2021). Safety was assessed through 6 months.

Results

Between April 27, 2021, and January 11, 2022, 2582 participants were randomized. In the primary efficacy analysis, RT-PCR-confirmed symptomatic COVID-19 occurred in 3/175 (1.7%) vs 12/176 (6.8%) adintrevimab- and placebo-treated PEP participants, respectively (74.9% relative risk reduction [RRR]; standardized risk difference, −5.0%; 95% CI, −8.87% to −1.08%; P = .0123) and in 12/752 (1.6%) vs 40/728 (5.5%) adintrevimab- and placebo-treated PrEP participants, respectively (71.0% RRR; standardized risk difference, −3.9%; 95% CI, −5.75% to −2.01%; P < .0001). In a prespecified exploratory analysis of 428 PrEP participants randomized after the emergence of Omicron, adintrevimab reduced RT-PCR-confirmed symptomatic COVID-19 by 40.6% (standardized risk difference −8.4%; 95% CI, −15.35% to −1.46%; nominal P = .0177) vs placebo. Adintrevimab was well tolerated, with no serious drug-related adverse events reported.

Conclusions

A single intramuscular injection of adintrevimab provided prophylactic efficacy against COVID-19 due to susceptible variants without safety concerns.

Clinical trial registration. NCT04859517.
Plant stem cells under low oxygen: metabolic rewiring by phytoglobin underlies stem cell functionality
Authors: Mira Mohammed M , Hill Robert D , Hilo Alexander , Langer Matthias , Robertson Sean , Igamberdiev Abir U , Wilkins Olivia , Rolletschek Hardy , Stasolla Claudio
Published: June 2023

Root growth in maize (Zea mays L.) is regulated by the activity of the quiescent center (QC) stem cells located within the root apical meristem. Here, we show that despite being highly hypoxic under normal oxygen tension, QC stem cells are vulnerable to hypoxic stress, which causes their degradation with subsequent inhibition of root growth. Under low oxygen, QC stem cells became depleted of starch and soluble sugars and exhibited reliance on glycolytic fermentation with the impairment of the TCA cycle through the depressed activity of several enzymes, including pyruvate dehydrogenase (PDH). This finding suggests that carbohydrate delivery from the shoot might be insufficient to meet the metabolic demand of QC stem cells during stress. Some metabolic changes characteristic of the hypoxic response in mature root cells were not observed in the QC. Hypoxia-responsive genes, such as PYRUVATE DECARBOXYLASE (PDC) and ALCOHOL DEHYDROGENASE (ADH), were not activated in response to hypoxia, despite an increase in ADH activity. Increases in phosphoenolpyruvate (PEP) with little change in steady-state levels of succinate were also atypical responses to low-oxygen tensions. Overexpression of PHYTOGLOBIN 1 (ZmPgb1.1) preserved the functionality of the QC stem cells during stress. The QC stem cell preservation was underpinned by extensive metabolic rewiring centered around activation of the TCA cycle and retention of carbohydrate storage products, denoting a more efficient energy production and diminished demand for carbohydrates under conditions where nutrient transport may be limiting. Overall, this study provides an overview of metabolic responses occurring in plant stem cells during oxygen deficiency.
A kirigami-enabled electrochromic wearable variable-emittance device for energy-efficient adaptive personal thermoregulation
Authors: Chen Ting-Hsuan , Hong Yaoye , Fu Ching-Tai , Nandi Ankita , Xie Wanrong , Yin Jie , Hsu Po-Chun
Published: June 2023

For centuries, people have put effort to improve the thermal performance of clothing to adapt to varying temperatures. However, most clothing we wear today only offers a single-mode insulation. The adoption of active thermal management devices, such as resistive heaters, Peltier coolers, and water recirculation, is limited by their excessive energy consumption and form factor for long-term, continuous, and personalized thermal comfort. In this paper, we developed a wearable variable-emittance (WeaVE) device, enabling the tunable radiative heat transfer coefficient to fill the missing gap between thermoregulation energy efficiency and controllability. WeaVE is an electrically driven, kirigami-enabled electrochromic thin-film device that can effectively tune the midinfrared thermal radiation heat loss of the human body. The kirigami design provides stretchability and conformal deformation under various modes and exhibits excellent mechanical stability after 1,000 cycles. The electronic control enables programmable personalized thermoregulation. With less than 5.58 mJ/cm2 energy input per switching, WeaVE provides 4.9°C expansion of the thermal comfort zone, which is equivalent to a continuous power input of 33.9 W/m2. This nonvolatile characteristic substantially decreases the required energy while maintaining the on-demand controllability, thereby providing vast opportunities for the next generation of smart personal thermal managing fabrics and wearable technologies.
3D bioprinting—a model for skin aging
Authors: Ansaf Ryeim B , Ziebart Rachel , Gudapati Hemanth , Simoes Torigoe Rafaela Mayumi , Victorelli Stella , Passos Joao , Wyles Saranya P
Published: June 2023

Human lifespan continues to extend as an unprecedented number of people reach their seventh and eighth decades of life, unveiling chronic conditions that affect the older adult. Age-related skin conditions include senile purpura, seborrheic keratoses, pemphigus vulgaris, bullous pemphigoid, diabetic foot wounds and skin cancer. Current methods of drug testing prior to clinical trials require the use of pre-clinical animal models, which are often unable to adequately replicate human skin response. Therefore, a reliable model for aged human skin is needed. The current challenges in developing an aged human skin model include the intrinsic variability in skin architecture from person to person. An ideal skin model would incorporate innate functionality such as sensation, vascularization and regeneration. The advent of 3D bioprinting allows us to create human skin equivalent for use as clinical-grade surgical graft, for drug testing and other needs. In this review, we describe the process of human skin aging and outline the steps to create an aged skin model with 3D bioprinting using skin cells (i.e. keratinocytes, fibroblasts and melanocytes). We also provide an overview of current bioprinted skin models, associated limitations and direction for future research.
Science diplomacy from the Global South: the case of intergovernmental science organizations
Authors: Rüland Anna-Lena , Rüffin Nicolas , Cramer Katharina , Ngabonziza Prosper , Saxena Manoj , Skupien Stefan
Published: June 2023

Intergovernmental science organizations (IGSOs) address many challenges of the 21st century. Several countries of the Global South have joined established IGSOs or have created new ones. Yet we know little about their interests in IGSOs. Our study addresses this blind spot by investigating which objectives Southern actors pursue in IGSOs and under which conditions they are likely to achieve their objectives. Using insights from three strands of literature, we compare four IGSOs with Southern participation: the European Organization for Nuclear Research, the International Thermonuclear Experimental Reactor, the Square Kilometer Array, and the African Lightsource. We show that countries of the Global South pursue a multitude of political and scientific objectives in IGSOs, ranging from capacity-building to casting off political isolation. Moreover, we demonstrate that Southern countries have varying chances of attaining these objectives, depending on their scientific community, domestic politics, industrial capacities and in some cases geographic location as well as an IGSO’s maturity.
Fate and Efficacy of Engineered Allogeneic Stem Cells Targeting Cell Death and Proliferation Pathways in Primary and Brain Metastatic Lung Cancer
Authors: Moleirinho Susana , Kitamura Yohei , Borges Paulo S G N , Auduong Sophia , Kilic Seyda , Deng David , Kanaya Nobuhiko , Kozono David , Zhou Jing , Gray Jeffrey J , Revai-Lechtich Esther , Zhu Yanni , Shah Khalid
Published: June 2023

Primary and metastatic lung cancer is a leading cause of cancer-related death and novel therapies are urgently needed. Epidermal growth factor receptor (EGFR) and death receptor (DR) 4/5 are both highly expressed in primary and metastatic non-small cell lung cancer (NSCLC); however, targeting these receptors individually has demonstrated limited therapeutic benefit in patients. In this study, we created and characterized diagnostic and therapeutic stem cells (SC), expressing EGFR-targeted nanobody (EV) fused to the extracellular domain of death DR4/5 ligand (DRL) (EVDRL) that simultaneously targets EGFR and DR4/5, in primary and metastatic NSCLC tumor models. We show that EVDRL targets both cell surface receptors, and induces caspase-mediated apoptosis in a broad spectrum of NSCLC cell lines. Utilizing real-time dual imaging and correlative immunohistochemistry, we show that allogeneic SCs home to tumors and when engineered to express EVDRL, alleviate tumor burden and significantly increase survival in primary and brain metastatic NSCLC. This study reports mechanistic insights into simultaneous targeting of EGFR- and DR4/5 in lung tumors and presents a promising approach for translation into the clinical setting.
Mesenchymal Stem Cell-Extracellular Vesicle Therapy for Stroke: Scalable Production and Imaging Biomarker Studies
Authors: Son Jeong Pyo , Kim Eun Hee , Shin Eun Kyoung , Kim Dong Hee , Sung Ji Hee , Oh Mi Jeong , Cha Jae Min , Chopp Michael , Bang Oh Young
Published: June 2023

A major clinical hurdle to translate MSC-derived extracellular vesicles (EVs) is the lack of a method to scale-up the production of EVs with customized therapeutic properties. In this study, we tested whether EV production by a scalable 3D-bioprocessing method is feasible and improves neuroplasticity in animal models of stroke using MRI study. MSCs were cultured in a 3D-spheroid using a micro-patterned well. The EVs were isolated with filter and tangential flow filtration and characterized using electron microscopy, nanoparticle tracking analysis, and small RNA sequencing. Compared to conventional 2D culture, the production-reproduction of EVs (the number/size of particles and EV purity) obtained from 3D platform were more consistent among different lots from the same donor and among different donors. Several microRNAs with molecular functions associated with neurogenesis were upregulated in EVs obtained from 3D platform. EVs induced both neurogenesis and neuritogenesis via microRNAs (especially, miR-27a-3p and miR-132-3p)-mediated actions. EV therapy improved functional recovery on behavioral tests and reduced infarct volume on MRI in stroke models. The dose of MSC-EVs of 1/30 cell dose had similar therapeutic effects. In addition, the EV group had better anatomical and functional connectivity on diffusion tensor imaging and resting-state functional MRI in a mouse stroke model. This study shows that clinical-scale MSC-EV therapeutics are feasible, cost-effective, and improve functional recovery following experimental stroke, with a likely contribution from enhanced neurogenesis and neuroplasticity.
Multilocus phylogeny and historical biogeography of theCrematogaster inflata-group (Hymenoptera: Formicidae) in South-East Asia
Authors: Hosoishi Shingo , Maruyama Munetoshi , Yamane Seiki , Jaitrong Weeyawat , Hashim Rosli , Syaukani Syaukani , Sokh Heng , Itioka Takao , Meleng Paulus , Pham Thai Hong
Published: June 2023

A recent molecular phylogeny of the genus Crematogaster reclassified some members of the former subgenera Paracrema and Physocrema into the C. inflata-group, now comprised of five species: C. ampullaris, C. inflata, C. modiglianii, C. onusta and C. subcircularis. Here, a molecular analysis of the Crematogaster inflata-group and eight other species of the former subgenus Physocrema (C. aurita, C. difformis, C. mucronata, C. physothorax, C. sewardi, C. tanakai, C. vacca and C. yamanei) is conducted using a total of c. 4 kb of sequence data from six nuclear protein-coding genes and two mitochondrial genes. Monophyly of the C. inflata-group is strongly supported. A revised morphological delineation of the subgroups is proposed, supported by the molecular phylogeny: three morphologically distinct subgroups, the C. difformis-subgroup, the C. vacca-subgroup and the C. inflata-subgroup. Molecular dating and biogeographical analyses indicate that the C. inflata-group originated in the Sundaic region around the Middle Miocene 12 Mya and diversified from the Late Miocene to Pliocene. Ancestral state reconstructions indicate that the C. inflata-group diversified from an ancestor with a swollen propodeum and circular-shaped metapleural gland opening. Biogeographical reconstruction indicates that dispersal to peripheral areas and allopatry due to sea-level changes shaped the evolutionary history of the C. inflata-group.
Sensitivity of Puccinia triticina f. sp. tritici from China to Triadimefon and Resistance Risk Assessment
Authors: Ji Fan , Zhou Aihong , Liu Bofan , Liu Yue , Feng Yaoxuan , Wang Xiaodong , Huang Lili , Kang Zhensheng , Zhan Gangming
Published: June 2023

Wheat leaf rust, caused by Puccinia triticina f. sp. tritici (Pt), is distributed widely in wheat-producing areas and results in serious yield losses worldwide. In China, leaf rust has been largely controlled with a demethylation inhibitor (DMI) fungicide, triadimefon. Although high levels of fungicide resistance in pathogens have been reported, no field failure of wheat leaf rust to DMI fungicides has been reported in China. A resistance risk assessment of triadimefon to Pt was investigated in the present study. The sensitivity of 197 Pt isolates across the country to triadimefon was determined, and the density distribution of EC50 values (concentration at which mycelial growth is inhibited by 50%) showed a continuous multimodal curve because of the extensive use of this fungicide in wheat production, with a mean value of 0.46 μg/ml. The majority of the tested Pt isolates were sensitive to triadimefon, whereas 10.2% developed varying degrees of resistance. Characterization of parasitic fitness revealed that the triadimefon-resistant isolates exhibited strong adaptive traits in urediniospore germination rate, latent period, sporulation intensity, and lesion expansion rate. No correlation was observed between triadimefon and tebuconazole and hexaconazole, which have the similar mode of action, or pyraclostrobin and flubeneteram, which have different modes of action. Overexpression of the target gene Cyp51 led to the triadimefon resistance of Pt. The risk of resistance to triadimefon in Pt may be low to moderate. This study provided important data for fungicide resistance risk management against wheat leaf rust.
Association between vasomotor symptom frequency and weight gain in the Study of Women's Health Across the Nation
Authors: Gibson Carolyn J. , Shiozawa Aki , Epstein Andrew J. , Han Wei , Mancuso Shayna
Published: June 2023

Objective

The menopause transition is associated with weight gain in women. We examined whether changes in vasomotor symptom (VMS) frequency precede weight changes.

Methods

This longitudinal retrospective analysis included data from the multisite, multiethnic Study of Women's Health Across the Nation. Women in premenopause or perimenopause aged 42 to 52 years at baseline self-reported VMS frequency (hot flashes/night sweats) and sleep problems at up to 10 annual visits. Menopause status, weight, body mass index, and waist circumference were compared across visits. The primary objective was to measure the association between VMS frequency and weight gain using a lagged approach with first-difference regression models. Secondary objectives were to statistically quantify mediation by sleep problems and moderation by menopause status and explore the association between cumulative, 10-year VMS exposure and long-term weight gain.

Results

The primary analysis sample included 2,361 participants (12,030 visits; 1995-2008). Increased VMS frequency across visits was associated with subsequently increased weight (0.24 kg), body mass index (0.08 kg/m2), and waist circumference (0.20 cm). Cumulative exposure to a high frequency of VMS (≥6 d/2 wk) over 10 consecutive annual visits was associated with increases in weight measures, including a 3.0-cm increase in waist circumference. Contemporaneous sleep problems mediated no more than 27% of waist circumference increases. Menopause status was not a consistent moderator.

Conclusions

This study demonstrates that increases in VMS, onset of a high frequency of VMS, and persistent VMS symptoms over time may precede weight gain in women.
Blood and Hand Surface Lead in Veterinary Workers Using Lead Shielding During Diagnostic Radiography
Authors: Mayer Monique , Feng Tongchen , Sukut Sally , Wiebe Sheldon , Parker Sarah , Blakley Barry , Koehncke Niels
Published: June 2023

Objectives

The objectives are to compare lead blood concentrations in veterinary workers using lead shielding with concentrations in a control population, to measure hand surface lead before and after use of shielding, and to compare hand surface lead with and without the use of disposable gloves worn under hand shielding.

Methods

Blood and hand wipe samples were analyzed for lead using inductively coupled plasma mass spectrometry.

Results

There was no difference in blood lead between exposed and control groups. After lead glove use, 69% (18/26) of hand surface lead samples from workers not using disposable gloves were greater than 500 μg, 42% (11/26) were greater than 1000 μg, and 12% (3/26) were greater than 2000 μg.

Conclusions

If lead shielding use is unavoidable, disposable gloves should be worn, and skin should be decontaminated after use.
Feasibility of a Video Otoscope for Diagnosis of Otologic Pathology in the Pediatric Emergency Department
Authors: Nystrom Jennifer , Lo Charmaine B. , Helwig Sara , Wurtz Morgan , Scherzer Daniel J. , Moberly Aaron C. , Iyer Maya S.
Published: June 2023

Objectives

Performing pediatric otoscopy can be difficult secondary to patient compliance, which potentiates misdiagnosis and inaccurate treatment of acute otitis media. This study used a convenience sample to assess the feasibility of using a video otoscope for the examination of tympanic membranes in children presenting to a pediatric emergency department.

Methods

We obtained otoscopic videos using the JEDMED Horus + HD Video Otoscope. Participants were randomized to video or standard otoscopy, and a physician completed their bilateral ear examinations. In the video group, physicians reviewed otoscope videos with the patient's caregiver. The caregiver and physician completed separate surveys using a 5-point Likert Scale regarding perceptions of the otoscopic examination. A second physician reviewed each otoscopic video.

Results

We enrolled 213 participants in 2 groups (standard otoscopy, n = 94; video otoscopy, n = 119). We used Wilcoxon rank sum, Fisher exact test, and descriptive statistics to compare results across groups. For physicians, there were no statistically significant differences between groups with ease of device use, quality of otoscopic view, or diagnosis. There was moderate agreement between physician video otoscopic view satisfaction and slight agreement between physician video otologic diagnosis. Estimates of length of time to complete the ear examinations were longer more often for the video otoscope compared with standard for both caregivers (OR, 2.00; 95% confidence interval, 1.10–3.70; P = 0.02) and physicians (OR, 3.08; 95% confidence interval, 1.67–5.78; P < 0.01). There were no statistically significant differences between video and standard otoscopy with regard to caregiver perception of comfort, cooperation, satisfaction, or diagnosis understanding.

Conclusions

Caregivers perceive that video otoscopy and standard otoscopy are comparable in comfort, cooperation, examination satisfaction, and diagnosis understanding. Physicians made a wider range of more subtle diagnoses with the video otoscope. However, examination length of time may limit the JEDMED Horus + HD Video Otoscope's feasibility in a busy pediatric emergency department.
Selective Application of Blood Glucose Monitoring After Free Flap Surgery
Authors: Kim Ju Hee , Lee Kyeong-Tae
Published: June 2023

Background

For free-flap monitoring, physical examination still serves as the criterion standard. Blood glucose measurement (BGM) has been suggested to be useful in identifying flap perfusion status. Nonetheless, its routine use may not be cost-effective in real-world settings. This study aimed to share the experiences of using BGM for flap monitoring and suggest its potential indications.

Methods

Of cases of free flap reconstruction conducted between March 2017 and May 2021, those using BGM for flap monitoring were reviewed. Blood glucose measurement was selectively conducted for the following specific situations, which included encountering a flap showing a reddish discoloration and/or rapid capillary refilling time in the immediate postoperative period, monitoring discolored flaps after conducting a salvage operation, and conducting bloodletting therapy for salvaging congestive flaps. The clinical course and outcomes were evaluated.

Results

Of a total of 203 cases, 35 used BGM for flap monitoring in addition to clinical examination. In 29 cases, BGM was performed to distinguish early hyperemia from true venous insufficiency. All flaps showed BGM greater than 60 mg/dL with a mean value of 115.42, suggesting early hyperemia, and had uneventful postoperative courses. In 3 cases with already discolored flaps after a salvage operation, BGM was conducted 4 times serially every 3 hours and showed a mean value of 81.6 mg/dL with increasing trends. The flaps recovered completely. In the other 3 cases requiring bloodletting therapy, BGM was conducted an average of 11 times at a median interval of 7 hours. The bloodletting therapy was terminated with reference to the value of BGM when it showed greater than 60 mg/dL while the therapy was on hold. All flaps were successfully salvaged except one showing partial necrosis.

Conclusions

Blood glucose measurement may be helpful in assessing flap perfusion and decision making in certain clinical situations and may be useful as an ancillary tool for flap monitoring. Selective application of BGM may contribute to achieving optimal outcomes.
Effects of Different Levels of Surgical Separation on Neck Bulge and Swallowing Disorders during Endoscopic Thyroidectomy
Authors: Huo Jinlong , Guo Youming , Chen Chen , Zhao Lijin , Wen Kunming
Published: June 2023

Objective:

Our study aims to compare the effects of different levels of access on postoperative neck bulge and swallowing disorder and provide a better level for endoscopic thyroidectomy.

Materials and Methods:

The patients were selected retrospectively between March 2021 to September 2021 by the Department of Thyroid Surgery, Third Affiliated Hospital of Zunyi Medical University. They were divided into two groups according to the level of the free flap during surgery: group A (the superficial cervical fascial level) and group B (the superficial deep cervical fascial level). Age, sex, body mass index, diameter of the primary lesion, postoperative neck bulge, and swallowing disorders and other complications were compared between the two groups.

Results:

A total of 40 patients who underwent endoscopic unilateral lobectomy plus central region lymph node dissection were enrolled in our study. Twenty in group A and 20 in group B. The age, gender, body mass index, diameter, and the proportion of benign and malignant primary lesions were not significantly different between the two groups (P>0.05), and there was also no difference in thyroid function between the two groups (P>0.05). No significant differences were observed in terms of bleeding and operation time during the operation (P>0.05). There were also no statistical differences in terms of recurrent laryngeal nerve injury or hypoparathyroidism (P>0.05). However, patients in group B were superior to those in group A in the occurrence of neck bulge and swallowing disorders (P<0.05). These symptoms were most evident one month after surgery. Six months after the operation, only 4 patients in group B still complained of neck “swelling” and uncomfortable straining which did not resolve until 1 year after the operation. No statistical significance between long-term results and complication rates could be observed in either group.

Conclusion:

In endoscopic thyroidectomy, the superficial cervical fascial level may be a better option for reducing postoperative neck bulge and swallowing disorders, which needs further validation by conducting a large sample study.
Learning Curve of Multiport Robotic Cholecystectomy: A Cumulative Sum Analysis
Authors: Kudsi Omar Yusef , Kaoukabani Georges , Friedman Alexander , Bou-Ayash Naseem , Bahadir Jenna , Crawford Allison S. , Gokcal Fahri
Published: June 2023

Objective:

To establish the learning curve of multiport robotic cholecystectomy (MRC).

Patients and Methods:

A retrospective analysis of patients undergoing MRC was performed. A cumulative sum analysis helped define the learning curve through the evaluation of skin-to-skin (STS) time and postoperative complications rate. Direct comparison of variables was conducted between the phases.

Results:

Two hundred forty-five MRC cases were included. Average STS and console times were 50.6 and 29.9 minutes, respectively. Cumulative sum analysis established 3 phases with inflection points at cases 84th and 134th. A significant decrease in STS time was observed between the phases. Middle and late phases encompassed patients with higher comorbidities. Two conversions to open were recorded in the early phase. Postoperative complication rates were comparable among the early (2.5%), middle (6.8%), and late (5.6%) phases (P = 0.482).

Conclusion:

A steady decrease in STS time was observed across the 3 different phases established at the 84th and 134th patients.
Circulating lipid profiles are associated with cross-sectional and longitudinal changes of central biomarkers for Alzheimer’s disease
Authors: Kim Jun Pyo , Nho Kwangsik , Wang Tingting , Huynh Kevin , Arnold Matthias , Risacher Shannon L. , Bice Paula J. , Han Xianlin , Kristal Bruce S. , Blach Colette , Baillie Rebecca , Kastenmüller Gabi , Meikle Peter J. , Saykin Andrew J. , Kaddurah-Daouk Rima ,   Alzheimer’s Disease Neuroimaging Initiative,   Alzheimer’s Disease Metabolomics Consortium
Published: June 2023

Investigating the association of lipidome profiles with central Alzheimer’s disease (AD) biomarkers, including amyloid/tau/neurodegeneration (A/T/N), can provide a holistic view between the lipidome and AD. We performed cross-sectional and longitudinal association analysis of serum lipidome profiles with AD biomarkers in the Alzheimer’s Disease Neuroimaging Initiative cohort (N=1,395). We identified lipid species, classes, and network modules that were significantly associated with cross-sectional and longitudinal changes of A/T/N biomarkers for AD. Notably, we identified the lysoalkylphosphatidylcholine (LPC(O)) as associated with “A/N” biomarkers at baseline at lipid species, class, and module levels. Also, GM3ganglioside showed significant association with baseline levels and longitudinal changes of the “N” biomarkers at species and class levels. Our study of circulating lipids and central AD biomarkers enabled identification of lipids that play potential roles in the cascade of AD pathogenesis. Our results suggest dysregulation of lipid metabolic pathways as precursors to AD development and progression.
Hyperacute Prediction of Targeted Temperature Management Outcome After Cardiac Arrest
Authors: Hsu Jocelyn , Kim Han , Gong Kirby , Azad Tej D. , Stevens Robert D.
Published: June 2023

Abstract

Introduction

Targeted temperature management (TTM) has been associated with greater likelihood of neurological recovery among comatose survivors of cardiac arrest. However, the efficacy of TTM is not consistently observed, possibly due to heterogeneity of therapeutic response. The aim of this study is to determine if models leveraging multi-modal data available in the first 12 hours after ICU admission (hyperacute phase) can predict short-term outcome after TTM.

Methods

Adult patients receiving TTM after cardiac arrest were selected from a multicenter ICU database. Predictive features were extracted from clinical, physiologic, and laboratory data available in the hyperacute phase. Primary endpoints were survival and favorable neurological outcome, determined as the ability to follow commands (motor Glasgow Coma Scale [mGCS] of 6) upon discharge. Three machine learning (ML) algorithms were trained: generalized linear models (GLM), random forest (RF), and gradient boosting (XG). Models with optimal features from forward selection were 10-fold cross-validated and resampled 10 times.

Results

Data were available on 310 cardiac arrest patients who received TTM, of whom 183 survived and 123 had favorable neurological outcome. The GLM performed best, with an area under the receiver operating characteristic curve (AUROC) of 0.86 ± 0.04, sensitivity 0.75 ± 0.09, and specificity 0.77 ± 0.07 for the prediction of survival and an AUROC of 0.85 ± 0.03, sensitivity 0.71 ± 0.10, and specificity 0.80 ± 0.12 for the prediction of favorable neurological outcome. Features most predictive of both endpoints included lower serum chloride concentration, higher serum pH, and greater neutrophil counts.

Conclusion

In patients receiving TTM after cardiac arrest, short-term outcomes can be accurately discriminated using ML applied to data routinely collected in the first 12 hours after ICU admission. With validation, hyperacute prediction could enable personalized approach to clinical decision-making in the post-cardiac arrest setting.
TG468: A Text Graph Convolutional Network for Predicting Clinical Response to Immune Checkpoint Inhibitor Therapy
Authors: Wang Kun , Shi Jiangshan , Tong Xiaochu , Qu Ning , Kong Xiangtai , Ni Shengkun , Xing Jing , Li Xutong , Zheng Mingyue
Published: June 2023

Immunotherapy has achieved significant success in tumor treatment. However, due to disease heterogeneity, only a fraction of patients respond well to immune checkpoint inhibitor (ICI) treatment. To address this issue, we developed a Text Graph Convolutional Network (Text GCN) model called TG468 for clinical response prediction, which uses the patient’s whole exome sequencing (WES) data across different cohorts to capture the molecular profile and heterogeneity of tumors. TG468 can effectively distinguish survival time for patients who received ICI therapy and outperforms single gene biomarkers and TMB, indicating its strong predictive ability for the clinical response of ICI therapy. Moreover, the prediction results obtained from TG468 allow for the identification of immune status differences among specific patient types in the TCGA dataset. This rationalizes the model prediction results. Overall, TG468 could be a useful tool for predicting clinical outcomes and the prognosis of patients treated with immunotherapy. This could further promote the application of ICI therapy in the clinic.
iEEG-recon: A Fast and Scalable Pipeline for Accurate Reconstruction of Intracranial Electrodes and Implantable Devices
Authors: Lucas Alfredo , Scheid Brittany H. , Pattnaik Akash R. , Gallagher Ryan , Mojena Marissa , Tranquille Ashley , Prager Brian , Gleichgerrcht Ezequiel , Gong Ruxue , Litt Brian , Davis Kathryn A. , Das Sandhitsu , Stein Joel M. , Sinha Nishant
Published: June 2023

Background

Collaboration between epilepsy centers is essential to integrate multimodal data for epilepsy research. Scalable tools for rapid and reproducible data analysis facilitate multicenter data integration and harmonization. Clinicians use intracranial EEG (iEEG) in conjunction with non-invasive brain imaging to identify epileptic networks and target therapy for drug-resistant epilepsy cases. Our goal was to promote ongoing and future collaboration by automating the process of “electrode reconstruction,” which involves the labeling, registration, and assignment of iEEG electrode coordinates on neuroimaging. These tasks are still performed manually in many epilepsy centers. We developed a standalone, modular pipeline that performs electrode reconstruction. We demonstrate our tool’s compatibility with clinical and research workflows and its scalability on cloud platforms.

Methods

We createdIEEG-recon, a scalable electrode reconstruction pipeline for semi-automatic iEEG annotation, rapid image registration, and electrode assignment on brain MRIs. Its modular architecture includes three modules: a clinical module for electrode labeling and localization, and a research module for automated data processing and electrode contact assignment. To ensure accessibility for users with limited programming and imaging expertise, we packaged iEEG-recon in a containerized format that allows integration into clinical workflows. We propose a cloud-based implementation of iEEG-recon, and test our pipeline on data from 132 patients at two epilepsy centers using retrospective and prospective cohorts.

Results

We used iEEG-recon to accurately reconstruct electrodes in both electrocorticography (ECoG) and stereoelectroencephalography (SEEG) cases with a 10 minute running time per case, and ∼20 min for semi-automatic electrode labeling. iEEG-recon generates quality assurance reports and visualizations to support epilepsy surgery discussions. Reconstruction outputs from the clinical module were radiologically validated through pre- and post-implant T1-MRI visual inspections. Our use of ANTsPyNet deep learning approach for brain segmentation and electrode classification was consistent with the widely used Freesurfer segmentation.

Discussion

iEEG-recon is a valuable tool for automating reconstruction of iEEG electrodes and implantable devices on brain MRI, promoting efficient data analysis, and integration into clinical workflows. The tool’s accuracy, speed, and compatibility with cloud platforms make it a useful resource for epilepsy centers worldwide. Comprehensive documentation is available athttps://ieeg-recon.readthedocs.io/en/latest/

Graphical Abstract
TKSM: Highly modular, user-customizable, and scalable transcriptomic sequencing long-read simulator
Authors: Karaoglanoglu Fatih , Orabi Baraa , Flannigan Ryan , Chauve Cedric , Hach Faraz
Published: June 2023

Motivation

Transcriptomic long-read (LR) sequencing is an increasingly cost-effective technology for probing various RNA features. Numerous tools have been developed to tackle various transcriptomic sequencing tasks (e.g. isoform and gene fusion detection). However, the lack of abundant gold standard datasets hinders the benchmarking of such tools. Therefore, simulation of LR sequencing is an important and practical alternative to enable the assessment of these tools. While the existing LR simulators aim to imitate the sequencing machine noise and to target specific library protocols, they lack some important library preparation steps (e.g. PCR) and are difficult to modify to new and changing library preparation techniques (e.g. single-cell LRs).

Results

We present TKSM, a modular and scalable LR simulator. TKSM is designed so that each RNA modification step is targeted explicitly by a software module. This allows the user to assemble a simulation pipeline of any combination of TKSM modules to emulate the sequencing design the user is targeting. Additionally, the input/output of all the core modules of TKSM follow the same simple format (Molecule Description Format) allowing the user to easily extend TKSM with new modules targeting new library preparation steps.

Availability

TKSM is available as an open source software athttps://github.com/vpc-ccg/tksm.
The orientation of choroidal macrophage polarization significantly influences the development of myopia in murine models
Authors: Hou Jing , Ikeda Shin-ichi , Mori Kiwako , Jeong Heonuk , Torii Hidemasa , Negishi Kazuno , Tsubota Kazuo , Kurihara Toshihide
Published: June 2023

Myopia is a primary contributor to visual impairment and has emerged as a global public health concern. Evidence indicates that one of the main structural features of myopia is the corresponding decrease in choroidal thickness, and choroidal macrophages play an important role in maintaining the choroidal thickness. Nevertheless, the effect of choroidal macrophages on myopia remains unclear. Here, we discovered that the continuous intraperitoneal injection of clodronate liposomes depleted choroidal macrophages and leads to myopia, which confirmed that the presence of choroidal macrophages plays an important role in myopia development. Subsequently, based on the phenotypic characteristics of macrophages, experiments were designed to study the effects of different polarization directions of macrophages on myopia development. We found that lipopolysaccharides (LPS) injection can induce the polarization of choroidal M1 macrophages, thinning the choroidal thickness and resulting in myopia. Conversely, IL-4 or IL-13 injection causes choroidal M2 macrophage polarization, thickens the choroid, and suppresses the progression of myopia. Additionally, we demonstrated that the opposite effects of M1 and M2 macrophages on myopia development may be related to their impacts on choroidal thickness, inflammation, and oxidative stress response. These findings establish that choroidal macrophages are critically important in the development of myopia and provide new strategies for the development of myopic therapies.
takeoutgene expression is associated with temporal kin recognition
Authors: Potticary Ahva L. , McKinney Elizabeth C. , Moore Patricia J. , Moore Allen J.
Published: June 2023

A key component of parental care is avoiding killing and eating your own offspring. Many organisms commit infanticide but switch to parental care at the time when their own offspring would be expected, known as temporal kin recognition. It is unclear how such indirect kin recognition is so common across taxa. One possibility is that temporal kin recognition can be achieved by altering a simple mechanism, such as co-opting the regulation of timing and feeding in other contexts. Here we determine whethertakeout, a gene implicated in coordinating feeding, influences temporal kin recognition in the roundneck sexton beetle,Nicrophorus orbicollis. We find thattakeoutexpression is not associated with non-parental feeding changes resulting from hunger, or in the general switch to the full parental care repertoire. However, beetles that accepted and provided care to their offspring had a highertakeoutexpression than beetles that committed infanticide. Together, these data support the idea that the evolution of temporal kin recognition may be enabled by co-option of mechanisms that integrate feeding behaviour in other contexts.
Host starvation andin hospitedegradation of algal symbionts shape the heat stress response of theCassiopea-Symbiodiniaceae symbiosis
Authors: Toullec Gaëlle , Rädecker Nils , Pogoreutz Claudia , Banc-Prandi Guilhem , Escrig Stéphane , Genoud Christel , Olmos Cristina Martin , Spangenberg Jorge , Meibom Anders
Published: June 2023

Global warming is causing large-scale disruption of cnidarian-Symbiodiniaceae symbioses fundamental to major marine ecosystems, such as coral reefs. However, the mechanisms by which heat stress perturbs these symbiotic partnerships remain poorly understood. In this context, the upside-down jellyfishCassiopeahas emerged as a powerful experimental model system. We combined a controlled heat stress experiment with isotope labeling and correlative SEM–NanoSIMS imaging to show that host starvation is a central component in the chain of events that ultimately leads to the collapse of theCassiopeaholobiont. Heat stress caused an increase in catabolic activity and a depletion of carbon reserves in the unfed host, concurrent with a reduction in the supply of photosynthates from its algal symbionts. This state of host starvation was accompanied by pronouncedin hospitedegradation of algal symbionts, which may be a distinct feature of the heat stress response ofCassiopea. Interestingly, this loss of symbionts by degradation was to a large extent concealed by body shrinkage of the starving animals, resulting in what could be referred to as ’invisible’ bleaching. Overall, our study highlights the importance of the nutritional status in the heat stress response of theCassiopeaholobiont. Compared with other symbiotic cnidarians, the large mesoglea ofCassiopea, with its structural sugar and protein content, may constitute an energy reservoir capable of delaying starvation. It seems plausible that this anatomical feature at least partly contributes to the relatively high stress tolerance of these animals in our warming oceans.