bluuebunny/crossref_metadata_2025 huggingface dataset:
Fentanyl Test Strips for Harm Reduction: A Scoping Review
Authors: Kutscher Eric , Barber Grossi Marco , LaPolla Fred , Lee Joshua D.
Published: June 2024

Background

High potency synthetic opioids like fentanyl have continued to replace or contaminate the supply of illicit drugs in North America, with fentanyl test strips (FTSs) often used as a harm reduction tool for overdose prevention. The available evidence to support FTS for harm reduction has yet to be summarized.

Methods

A search of PubMed, Ovid Embase, and Web of Science was conducted in March 2023. A 2-stage review was conducted to screen by title and abstract and then by full text by 2 reviewers. Data were extracted from each study using a standardized template.

Results

A total of 91 articles were included, mostly from North America, predominantly reporting on FTS along with other harm reduction tools, and all conducted after 2016. No randomized controlled trials are reported. Robust evidence exists supporting the sensitivity and specificity of FTS, along with their acceptability and feasibility of use for people who use drugs and as a public health intervention. However, limited research is available on the efficacy of FTS as a harm reduction tool for behavior change, engagement in care, or overdose prevention.

Conclusions

Though FTSs are highly sensitive and specific for point of care testing, further research is needed to assess the association of FTS use with overdose prevention. Differences in FTS efficacy likely exist between people who use opioids and nonopioid drugs, with additional investigation strongly needed. As drug testing with point-of-care immunoassays is embraced for nonfentanyl contaminants such as xylazine and benzodiazepines, increased investment in examining overdose prevention is necessary.
Magnesium Sulfate Before Preterm Birth for Neuroprotection
Authors: Shepherd Emily S. , Goldsmith Shona , Doyle Lex W. , Middleton Philippa , Marret Stéphane , Rouse Dwight J. , Pryde Peter , Wolf Hanne T. , Crowther Caroline A.
Published: June 2024

OBJECTIVE:

To systematically review the evidence for the effectiveness and safety of magnesium sulfate as a fetal neuroprotective agent when given to individuals at risk of preterm birth.

DATA SOURCES:

We searched Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov, the World Health Organization International Clinical Trials Registry Platform (through March 17, 2023), and reference lists of relevant studies.

METHODS OF STUDY SELECTION:

Randomized controlled trials (RCTs) assessing magnesium sulfate for fetal neuroprotection in pregnant participants at risk of imminent preterm birth were eligible. Two authors assessed RCTs for inclusion, extracted data, and evaluated risk of bias, trustworthiness, and evidence certainty (GRADE [Grading of Recommendations Assessment, Development and Evaluation]).

TABULATION, INTEGRATION, AND RESULTS:

We included six RCTs (5,917 pregnant participants and 6,759 fetuses at less than 34 weeks of gestation at randomization). They were conducted in high-income countries (two in the United States, two across Australia and New Zealand, and one each in Denmark and France) and commenced between 1995 and 2018. Primary outcomes: up to 2 years of corrected age, magnesium sulfate compared with placebo reduced the risk of cerebral palsy (risk ratio [RR] 0.71, 95% CI, 0.57–0.89; six RCTs, 6,107 children) and death or cerebral palsy (RR 0.87, 95% CI, 0.77–0.98; six RCTs, 6,481 children) (high-certainty evidence). Magnesium sulfate had little or no effect on death up to 2 years of corrected age (moderate-certainty evidence) or these outcomes at school age (low-certainty evidence). Although there was little or no effect on death or cardiac or respiratory arrest for pregnant individuals (low-certainty evidence), magnesium sulfate increased adverse effects severe enough to stop treatment (RR 3.21, 95% CI, 1.88–5.48; three RCTs, 4,736 participants; moderate-certainty evidence). Secondary outcome: magnesium sulfate reduced the risk of severe neonatal intraventricular hemorrhage (moderate-certainty evidence).

CONCLUSION:

Magnesium sulfate for preterm fetal neuroprotection reduces cerebral palsy and death or cerebral palsy for children. Further research is required on longer-term benefits and harms for children, effect variation by participant and treatment characteristics, and the generalizability of findings to low- and middle-income countries.

SYSTEMATIC REVIEW REGISTRATION:

The review protocol was based on a standard Cochrane Pregnancy and Childbirth template and our previous Cochrane Systematic Review (doi: 10.1002/14651858.CD004661.pub3; published before the introduction of PROSPERO).
Right atrial angiosarcoma presenting with pseudoaneurysm and rupture: a case report
Authors: Sadiq Abid M. , Shanmugam Karthik , Govind Satish C. , Raj Vimal , Sahetia Khushboo , G. Raghu M. , Raut Barendra K.
Published: June 2024

Cardiac sarcomas are the predominant type of malignant primary cardiac tumors, especially in cases where the patients are <50 years of age and have a poor prognosis, with a 5-year survival rate of less than 15%. Cardiac angiosarcomas are a common type of cardiac sarcoma. Cardiac angiosarcoma is a highly aggressive tumour, with approximately 75% of the cases originating in the right atrium, and has a higher incidence in males than in females. The present case report describes a 31-year-old woman who was initially suspected of having tuberculous pericarditis and was treated with anti-tuberculous medication. However, cardiac imaging analysis revealed a right atrial pseudoaneurysm with spontaneous rupture of the lateral right atrium. The patient underwent surgical exploration, in which a large mass infiltrating the right atrium, right ventricle, and right pleura with the ruptured right atrium was discovered. Mass excision and right atrial repair were performed, and the patient was admitted to the intensive care unit; however, she subsequently succumbed to her illness. Histopathological examination confirmed the diagnosis of cardiac angiosarcoma. Primary cardiac angiosarcoma is a rare and aggressive tumor that is difficult to diagnose. Most patients have systemic metastasis and a poor prognosis at the time of presentation. A confirmatory diagnosis was made after sample collection, highlighting the need to improve diagnostic and therapeutic methods for this disease.
Patient-Reported Outcomes and Higher Order Aberrations Following Topography-Guided Femtosecond Laser-Assisted In Situ Keratomileusis
Authors: Ahluwalia Aneesha , Ma Kevin K. , Manche Edward E.
Published: June 2024

Purpose:

To examine patient-reported outcomes and higher order aberrations following topography-guided laser-assisted in situ keratomileusis (LASIK).

Methods:

This was a prospective, nonrandomized observational study at a single academic center. Sixty eyes from 30 patients underwent bilateral topography-guided femtosecond LASIK for correction of myopia using the VisuMax 500 femtosecond laser (Zeiss; Oberkochen, Germany) and Allegretto Wave Eye-Q 400 Hz Excimer Laser (Alcon/Wavelight; Erlangen, Germany) with the Contoura topography system (Alcon; Geneva, Switzerland) for topography-modified refraction. The main outcomes of this study were higher order aberrations (HOAs) and results from the Patient-Reported Outcomes with LASIK questionnaire.

Results:

There was a small, significant increase in HOA root mean square, spherical aberration, and coma at 1, 3, 6, and 12 months following topography-guided LASIK (all P < 0.05), but no change in trefoil. In addition, self-reported worry related to vision (P < 0.001) and ability to perform activities (P < 0.001) significantly improved after surgery. The prevalence of double images, glare, halos, or starbursts decreased from 73% preoperatively to 56%, and no participants reported “very” or “extremely” bothersome visual symptoms after 12 months. Dry eye symptoms per Ocular Surface Disease Index score decreased significantly at 6 (P = 0.01) and 12 (P = 0.002) months after surgery. There was a 100% satisfaction rate with visual outcomes and duration of time to improvement in vision following the procedure.

Conclusions:

Although there was an increase in HOAs following topography-guided LASIK, there were significant improvements in the presence of double images, glare, halos, and starbursts and vision-related quality-of-life metrics. Overall satisfaction rates in this study were high.
COVID-19 Drug Treatments Are Prone to Sequestration in Extracorporeal Membrane Oxygenation Circuits: An Ex Vivo Extracorporeal Membrane Oxygenation Study
Authors: Dhanani Jayesh A. , Shekar Kiran , Parmar Dinesh , Lipman Jeffrey , Bristow Debra , Wallis Steven C. , Won Hayoung , Sumi Chandra D. , Abdul-Aziz Mohd H. , Roberts Jason A.
Published: June 2024

Drug treatments for coronavirus disease 2019 (COVID-19) dramatically improve patient outcomes, and although extracorporeal membrane oxygenation (ECMO) has significant use in these patients, it is unknown whether ECMO affects drug dosing. We used an ex vivo adult ECMO model to measure ECMO circuit effects on concentrations of specific COVID-19 drug treatments. Three identical ECMO circuits used in adult patients were set up. Circuits were primed with fresh human blood (temperature and pH maintained within normal limits). Three polystyrene jars with 75 ml fresh human blood were used as controls. Remdesivir, GS-441524, nafamostat, and tocilizumab were injected in the circuit and control jars at therapeutic concentrations. Samples were taken from circuit and control jars at predefined time points over 6 h and drug concentrations were measured using validated assays. Relative to baseline, mean (± standard deviation [SD]) study drug recoveries in both controls and circuits at 6 h were significantly lower for remdesivir (32.2% [±2.7] and 12.4% [±2.1], p < 0.001), nafamostat (21.4% [±5.0] and 0.0% [±0.0], p = 0.018). Reduced concentrations of COVID-19 drug treatments in ECMO circuits is a clinical concern. Remdesivir and nafamostat may need dose adjustments. Clinical pharmacokinetic studies are suggested to guide optimized COVID-19 drug treatment dosing during ECMO.
Complete versus partial revascularization for older adults with acute coronary syndrome: a meta-analysis and systematic review of randomized and multivariable adjusted data
Authors: Carvalho Ferreira André Luiz , Garcez de Carvalho Feitoza Luanna Paula , Cáceres Lessa Ana Yasmin , Chaves de Oliveira Juliana , Chierici Pereira Lucas , Benitez Gonzalez Maria Esther , Coelho Pessoa Lima Ana Emanuela , Ferreira Neves Henrique Alexsander , Mota Guida Camila
Published: June 2024

Background

Evidence from randomized studies support complete over culprit-only revascularization for patients with acute coronary artery syndrome (ACS) and multivessel coronary artery diseases (MVD). Whether these findings extend to elderly patients, however, has not been thoroughly explored.

Methods

We conducted a systematic review and meta-analysis comparing clinical outcomes of elderly individuals (defined as age ≥75 years) with ACS and MVD submitted to complete vs partial-only percutaneous coronary intervention (PCI). PubMed, Embase, and Cochrane were searched. We computed pooled hazard ratios with 95% confidence intervals (CI) to preserve time time-to-event data.

Results

We included 7 studies, of which 2 were RCT and 5 were multivariable adjusted cohorts, comprising a total 10 147, of whom 43.8% underwent complete revascularization. As compared with partial-only PCI, complete revascularization was associated with a lower all-cause mortality (hazard ratio 0.71; 95% CI 0.60–0.85; P < 0.01), cardiovascular mortality (hazard ratio 0.64; 95% CI 0.52–0.79; P < 0.01), and recurrent myocardial infarction (hazard ratio 0.65; 95% CI 0.50–0.85; P < 0.01). There was no significant difference between groups regarding the risk of revascularizations (hazard ratio 0.80; 95% CI 0.53–1.20; P = 0.28).

Conclusion

Among elderly patients with ACS and multivessel CAD, complete revascularization is associated with a lower risk of all-cause mortality, cardiovascular mortality, and recurrent myocardial infarction.
Clinicopathological features, prognostic factors, and prognostic survival prediction in patients with extrahepatic bile duct cancer liver metastasis
Authors: Huang Xianyu , Chen Wenhui , Liu Jiaxin , Liao Yonghui , Cai Jia , Zhong Dingwen
Published: June 2024

Purpose

Extrahepatic bile duct cancer (EBDC) is a compound malignant tumor mainly consisting of extrahepatic cholangiocarcinoma and gallbladder carcinoma. Most EBDC patients are diagnosed at an advanced stage characterized by distant metastases, and the liver is one of the common sites of metastasis. Hence, the purpose of this study is to investigate the clinicopathological features, identify prognostic risk factors, and assess the long-term prognosis of extrahepatic bile duct cancer liver metastasis (EBDCLM).

Methods

We identified 1922 eligible EBDCLM patients from the SEER database.Cox regression models were used to predict independent prognostic factors for overall survival (OS) and cancer-specific survival (CSS),and Kaplan–Meier survival curves were drawn. A nomogram was constructed based on the results of multivariate Cox analysis, and the predictive effect of the nomogram was evaluated.

Results

Age, surgery, chemotherapy, brain metastasis, and lung metastasis were common independent prognostic factors for OS and CSS, and radiotherapy and bone metastasis were independent prognostic factors for CSS. The Kaplan–Meier survival curves showed a significant increase in survival for patients aged less than or equal to 70 years, undergoing surgery and chemotherapy, and without lung metastases. The results showed that the nomogram constructed by us had good predictability and ha d strong clinical application value.

Conclusion

Our study identified age, surgery, chemotherapy, brain metastasis, and lung metastasis as independent prognostic factors for EBDCLM patients. The nomogram can accurately predict the survival probability, which is helpful for clinicians to assess the prognosis of patients with advanced EBDC and provide personalized clinical decisions.
Trans-abdominal fetal reduction in higher order multiple pregnancies: a pioneer cohort retrospective study in Nepal
Authors: Paudel Sharma , Dahal Prajwal , Pant Padam Raj , Subedi Nilam
Published: June 2024

Objective:

To share the initial experience of trans-abdominal multifetal pregnancy reduction (MFPR) in Nepal.

Method:

The procedure was performed in 108 patients in a private hospital over a period of 3 years. Under ultrasound guidance, intracardiac injection of 0.2–3.0 ml of 15% w/v (2 mEq/ml) potassium chloride (KCl) was administered via trans-abdominal route.

Results:

A total of 108 fetal reduction procedures were carried out at the seventh to fifteenth weeks of gestation, a maximum of 44 (40.7%) of which were done at the ninth to tenth weeks of gestation. A total of 123 fetuses were reduced. Out of total 108 multifetal pregnancies, 96 (88.8%) were due to in-vitro fertilization (IVF). Eighty-five pregnancies (78.7%) underwent reduction from triplet to twin. The second-time reduction was needed in five cases. Two attempts (in the same sitting) were required in three cases. The inadvertent demise of the second fetus was noted in three cases of dichorionic tri-amniotic triplet pregnancy.

Conclusion:

Ultrasound-guided trans-abdominal fetal reduction performed between the seventh and twelfth weeks of gestation is safe and effective.
Trajectories of pain and depressive symptoms among people living with low back pain during the COVID-19 pandemic: a 24-month longitudinal study
Authors: Angarita-Fonseca Adriana , Roy Mathieu , Lacasse Anaïs , Léonard Guillaume , Rainville Pierre , Marin Marie-France , Tufa Iulia , Gentile Erika L. , Pagé M. Gabrielle ,   on behalf of the Quebec Back Pain Consortium
Published: June 2024

Introduction: We explored trajectories of pain intensity and depressive symptoms over the first 24 months of the pandemic in people with low back pain.

Methods: This longitudinal study was conducted alongside the Quebec Low Back Pain Study. Starting in April 2020 and every 3 months until July 2022, 291 participants completed an online survey. Group-based trajectory modeling was used to identify patterns of pain intensity and depressive symptoms. Onset outbreak characteristics were then put in relation with trajectory groups using multivariate logistic regression.

Results: The analysis revealed 5 trajectories of pain intensity and depressive symptoms, respectively. The pain trajectories were stable mild (n = 17, 5.8%); stable moderate (n = 103, 35.4%); stable severe (n = 81, 27.8%); U-shape (n = 24, 8.3%), and inverted U-shape (n = 66, 22.7%). The trajectories of depressive symptoms were stable none (n = 58, 19.9%); stable very mild (n = 61, 21.0%); stable mild (n = 85, 29.2%); stable moderate (n = 59, 21.7%); and severe slightly improving (n = 24, 8.3%). Pre-COVID everyday/nearly everyday pain, average pain intensity, and widespread bodily pain were predictive of pain trajectory groups. Higher pre-COVID depression, acute stress disorder, and lockdown measures-related stress were associated with moderate/severe depressive trajectories.

Discussion: Our findings indicated relative stability of pain and depressive symptoms among participants during the COVID-19 pandemic but also highlighted subgroups of people who experienced temporary deterioration or improvement over the first months of the pandemic that then reverted back to baseline levels. Modifiable risk factors were identified before the onset of the pandemic, which could give preventive measures in targeted populations.
Messaging about HIV Transmission Risk When Viral Load Is Undetectable: Reactions and Perceived Accuracy among US Sexual Minority Men
Authors: Calabrese Sarah K. , Zaheer Myra A. , Flores Justino J. , Kalwicz David A. , Modrakovic Djordje X. , Rao Sharanya , Dovidio John F. , Zea Maria Cecilia , Eaton Lisa A.
Published: June 2024

Background:

Scientific evidence indicates that HIV viral suppression to an undetectable level eliminates sexual transmission risk ("Undetectable=Untransmittable” or “U=U”). However, U=U messaging has been met with skepticism among sexual minority men (SMM) and others. In this survey-based experiment, we manipulated messaging about HIV risk and examined reactions and perceived message accuracy among US SMM.

Methods:

SMM living with HIV (n=106) and HIV-negative/status-unknown SMM (n=351) participated in an online survey (2019-2020). Participants were randomly assigned to one of three messaging conditions, which varied by level of HIV sexual transmission risk associated with an undetectable viral load (No Risk [U=U]/Low Risk/Control). Participants reported reactions, message accuracy, and reasons for perceiving inaccuracy. We coded open-response data (reactions and reasons) into conceptual categories (e.g., “Enthusiasm”). We compared reactions, accuracy ratings, and reasons by condition and serostatus.

Results:

In the No Risk Condition, common reactions were Enthusiasm (40.0%), Skepticism/Disagreement (20.0%), and Agreement (19.4%), reactions common to comparison conditions. A higher percentage of HIV-negative/status-unknown participants (24.1%) expressed Skepticism/Disagreement in the No Risk Condition compared with other conditions (3.2%-9.7%). Participants living with HIV were more likely than HIV-negative/status-unknown participants to perceive all messages as accurate. In the No Risk Condition, common reasons for perceiving inaccuracy were Risk Misstated (46.1%), Oversimplified/Caveats Needed (17.1%), and Personal Unfamiliarity/Uncertainty (14.5%), reasons common to comparison conditions. Across conditions, 10.3% of participants attributed message inaccuracy to misdefinition of undetectable.

Conclusion:

Most SMM reacted favorably to U=U messaging. However, many—especially HIV-negative/status-unknown SMM—expressed skepticism. Interventions are needed to enhance U=U understanding and acceptance.
Role of Plastic Surgery in the Treatment of Titanium Mesh Exposure Following Cranioplasty
Authors: Wang Hui , Li Nan , Bao Qi , Shao Zheren , Hu Xueqing , Ma Qi
Published: June 2024

Background:

Titanium mesh cranioplasty is the most common strategy for the repair of skull defects. However, as the frequency of cranioplasty increases, the incidence of titanium mesh exposure following cranioplasty increases as well. This study aimed to investigate the methods and outcomes of plastic surgery in the management of titanium mesh exposure following cranioplasty.

Methods:

Patients with titanium mesh exposure following cranioplasty were retrospectively selected from January 2016 to August 2021. Titanium mesh exposure was corrected with reconstructive plastic surgery, including skin grafting, expander insertion, partial removal of the exposed mesh, replacement of the mesh, or flap transplantation.

Results:

This study included 21 patients with titanium mesh exposure with surgical site infection and a variant of scalp deformity. The age of the patients ranged from 18 to 74 years, with the mean age being 54 years. All patients underwent reconstructive plastic surgery and exhibited complete wound healing. The follow-up period ranged from 17 to 90 months. One patient experienced titanium mesh re-exposure and subsequently underwent an additional procedure for the partial removal of the exposed mesh. No serious complications were observed postoperatively.

Conclusion:

Reconstructive plastic surgery can facilitate wound healing at the titanium mesh exposure site following cranioplasty. However, an individualized treatment strategy is required for each patient, and complications should be managed by adopting standard measures.
Sequential Assessment of External Nasal Deviation Angle Changes in Patients With a Deviated Nose Who Underwent Bilateral Osteotomy
Authors: Jo Ki Hun , Lee So Yeon , Kwon Jae Hwan , Kim Jooyeon
Published: June 2024

Objective:

A deviated nose is traditionally classified as bony, cartilaginous, or combined deviation. Osteotomy is commonly used to correct bony deviation, and accurate surgical techniques and postoperative patient management are important for favorable outcomes. The authors investigated the change in the external nasal deviation angle over time using sequential clinical photographs to identify the optimal postoperative follow-up duration.

Methods:

Medical records and sequential standardized clinical photographs of 22 patients who underwent bilateral medial and lateral osteotomies without dorsal augmentation from January 1, 2014 to May 31, 2021, were retrospectively reviewed. Clinical photographs were classified into 4 periods: “a” preoperative, “b” postoperative day (POD) ≤3 weeks, “c” POD ≤9 weeks, and “d” POD >9 weeks. The angle of deviation (AoD) was measured in both frontal and chin-on-chest views for each period. Differences in AoD between temporally adjacent periods were analyzed.

Results:

Nineteen men and 3 women (mean age: 28.8 y) were included. Thirteen patients showed rightward deviation, whereas 9 showed leftward deviation. Eleven patients underwent surgery through an endonasal approach, whereas the other 11 underwent surgery through an external approach. In the frontal view, AoD differences (mean ± SD) between periods “a” and “b,” “b” and “c,” and “c” and “d” were 5.79 ± 3.36 degrees (P < 0.001), 1.44 ± 1.14 degrees (P < 0.001), and 1.07 ± 1.24 degrees (P < 0.05), respectively. In the chin-on-chest view, the values were 5.17 ± 2.69 degrees (P < 0.001), 2.06 ± 2.63 degrees (P < 0.001), and 1.46 ± 1.31 degrees (P < 0.001), respectively. No statistically significant difference in AoD differences was observed between the two approaches.

Conclusions:

Angle of deviation can change even 9 weeks after bilateral osteotomy. Thus, long-term follow-up using sequential clinical photographs is mandatory. If needed, close follow-up with early postoperative interventions may be required. The chin-on-chest view showed better sensitivity for assessing AoD than the frontal view.
Cleft Lip and Palate Surgery at a Rural African Hospital: A 13-Year Experience From Western Kenya
Authors: Rhodes Isaiah J. , Zhang Ashley , Arbuiso Sophia , Alston Chase C. , Medina Samuel J. , Liao Matthew , Nthumba Joseph , Chesang Patricia , Hayden Giles , Rhodes William R. , Otterburn David M.
Published: June 2024

Introduction:

Most studies on the treatment of cleft lip and palate (CLP) in low-income and middle-income countries have reported on the experience of urban centers or surgical mission trips to rural locations. There is a paucity of literature on the experience of local teams providing orofacial cleft surgery in rural Sub-Saharan Africa. This study reports the efficacy and cost-effectiveness of cleft surgery performed by an all-local team in rural Kenya.

Methods:

A retrospective chart review was performed on all patients who received CLP repair at Kapsowar Hospital between 2011 and 2023. Information regarding patient age, sex, cleft etiology, surgical management, and home location was retrieved. For the most recent year of study (2023), the authors performed a financial audit of all costs related to the performance of unilateral cleft lip surgery. Descriptive statistics were performed.

Results:

The authors identified 381 CLP surgeries performed on 311 patients (197 male, 63.3%). The most common etiology of the cleft was left unilateral (28.3%). The average age of primary lip repair decreased from 46.3 months in 2008 to 2009 to 20.2 months in 2022 to 2023 (P<0.001). The average age of primary cleft palate repair decreased from 38.0 months in 2008 to 2009 to 25.3 months in 2022 to 2023 (P<0.001). Patients traveled from 23 districts to receive treatment. Age of treatment was not different when distinguished by sex, county poverty level, or travel time from the hospital. The total costs associated with cleft lip repair was $201.6.

Conclusions:

Adequately staffed hospitals in rural locations can meaningfully address a regional CLP backlog more cost-effectively than surgical mission trips.
Long-Term Follow-Up of Apert Syndrome Following Mid-Face Advancement: More Than 3 Decades Later
Authors: Deek Roland , Moore Mark
Published: June 2024

Apert syndrome is characterized by craniosynostosis, a hypoplastic mid-face, skeletal abnormalities, symmetric syndactyly of the hands and feet, and a degree of neurocognitive impairment. Long-term outcomes of patients who have undergone surgical correction of Apert syndrome are limited. The authors present the case of a 73-year-old female with Apert syndrome, with follow-up of more than 3 decades following a fronto-orbital advancement and Le Fort III advancement. Clinical and radiologic images demonstrate a degree of skeletal resorption and relapse that is likely unavoidable. This provides insight into the long-term skeletal stability and esthetic outcomes for patients with Apert syndrome.
Optic Neuritis After COVID-19 Vaccination: A Case Series and a Review of Literature
Authors: Yang Sheng-Chi , Lee Yu-Kuei , Chuang Ming-Tsung , Hsu Huai-Wen , Chang Hsu-Yang , Chang Yi-Sheng
Published: June 2024

Background:

The coronavirus disease (COVID-19) pandemic broke out in March 2020, causing tremendous damage to public health and more than 6 million deaths. After authorization for the emergency use of COVID-19 vaccines, various adverse events have been reported, including optic neuritis. COVID-19 vaccination was implemented in Taiwan in March 2021.

Methods:

We report patients who developed optic neuritis after COVID-19 vaccination at one university-affiliated tertiary hospital, between March 2021 and December 2022. We also provided a literature review of optic neuritis cases after COVID-19 vaccination.

Results:

Five patients who developed optic neuritis after COVID-19 vaccination have been identified. Four brands of vaccine used were as follows: Moderna, Pfizer-BioNTech, Medigen, and Oxford AstraZeneca. Optic neuritis developed after the first dose of vaccination in 4 patients, whereas in 1 patient, it developed after the second shot. In the 3 patients with poor initial visual acuity, intravenous methylprednisolone pulse therapy achieved substantial improvement.

Conclusions:

Optic neuritis is a rare but potentially vision-threatening adverse effect of COVID-19 vaccination. We suggest early diagnosis and treatment to maximize visual outcomes.
Successful Treatment of Both Refractory Neuroleptic Malignant Syndrome and Subsequent Catatonia With Electroconvulsive Therapy in a Patient With Suspected Kufs Disease
Authors: Celik Sacha , de Gennaro Veronica , C.-P.-Silva João , Swierkosz-Lenart Kevin , von Gunten Armin
Published: June 2024

We describe a patient suffering from probable Kufs disease who developed a neuroleptic malignant syndrome (NMS) after use of an antipsychotic agent over some weeks during hospitalization due to neuropsychiatric symptoms. Transferred to the neurology department, the patient quickly developed catatonic features. She did not respond to usual medical treatment but did respond to electroconvulsive therapy (ECT). The patient worsened following a nosocomial SARS-CoV-2 infection but improved again during a second course of ECT. We discuss Kufs disease as a potential risk factor for NMS and address the link between NMS and catatonia as well as the indication for ECT in both disorders. We also discuss the impact of SARS-CoV-2 infection on the clinical outcome. We describe the long recovery process and the secondary worsening of the patient on a cognitive level.
An open-source alignment method for multichannel infinite-conjugate microscopes using a ray transfer matrix analysis model
Authors: Cairns Gemma S. , Patton Brian R.
Published: June 2024

Multichannel, infinite-conjugate optical systems easily allow implementation of multiple image paths and imaging modes into a single microscope. Traditional optical alignment methods which rely on additional hardware are not always simple to implement, particularly in compact open-source microscope designs. We present here an alignment algorithm and process to position the lenses and cameras in a microscope using only image magnification measurements. We show that the resulting positioning accuracy is comparable to the axial resolution of the microscope. Ray transfer matrix analysis is used to model the imaging paths when the optics are both correctly and incorrectly aligned. This is used to derive the corresponding image magnifications. We can then extract information about the lens positions using simple image-based measurements to determine whether there is misalignment of the objective lens to sample distance (working distance) and with what magnitude and direction the objective lens needs to be adjusted. Using the M4All open-source 3D printable microscope system in combination with the OpenFlexure microscope, we validate the alignment method and highlight its usability. We provide the model and an example implementation of the algorithm as an open-source Jupyter Notebook.

This article is part of the Theo Murphy meeting issue ‘Open, reproducible hardware for microscopy’.
FOXP3+ Regulatory T Cells Require TBET to Regulate Activated CD8+ T Cells During Recovery from Influenza Infection
Authors: Mambetsariev Nurbek , Torres Acosta Manuel A. , Liu Qianli , Flores Carla P. Reyes , Joudi Anthony M. , Helmin Kathryn A. , Gurkan Jonathan K. , Steinert Elizabeth M. , Morales-Nebreda Luisa , Singer Benjamin D.
Published: June 2024

FOXP3+ regulatory T (Treg) cells are necessary to coordinate resolution of lung inflammation and a return to homeostasis after respiratory viral infections, but the specific molecular requirements for these functions and the cell types governed by Treg cells remain unclear. This question holds significance as clinical trials of Treg cell transfer therapy for respiratory viral infection are being planned and executed. Here, we report causal experiments in mice determining that Treg cells are necessary to control the numbers of activated CD8+ T cells during recovery from influenza infection. Using a genetic strategy paired with adoptive transfer techniques, we determined that Treg cells require the transcription factor TBET to regulate these potentially pro-inflammatory CD8+ T cells. Surprisingly, we found that Treg cells are dispensable for the generation of CD8+ lung tissue resident-memory T (Trm) cells yet similarly influence the transcriptional programming of CD8+ Trm and activated T cells. Our study highlights the role of Treg cells in regulating the CD8+ T cell response during recovery from influenza infection.
Cannabinoid CB2 receptors enhance high-fat diet evoked peripheral neuroinflammation
Authors: Hosoki Haruka , Asahi Toru , Nozaki Chihiro
Published: June 2024

It is known that cannabinoid type 2 (CB2) receptor has anti-inflammatory role, therefore animals without CB2 receptors show enhanced inflammation and pain in the model of chronic pain e.g. neuropathic pain. We previously proposed the upregulated leptin signaling at the peripheral nerve as one of the underlying molecular mechanisms of pain exacerbation in nerve-injured CB2 knockouts, as they displayed robust upregulation of leptin receptors and leptin signaling in peripheral nerve. Due to these past results we hypothesized that CB2 receptor deficiency might also modify the peripheral neuroinflammation lead by chronic exposure to high fat diet (HFD). Interestingly, CB2 knockout animals showed the significant resistance to the HFD-induced neuroinflammation. Namely, 5-week feeding of HFD induced substantial hypersensitivity in WT animals, while tactile sensitivity of HFD-fed CB2 knockouts remained intact. HFD-fed WT animals also displayed the robust upregulation of chemokine CXCR4 expression with increased macrophage infiltration, which was never observed in HFD-fed CB2 knockout mice. Moreover, 5-week HFD-exposure lead significant increase of CD11b+Ly6G-Ly6Chighcells and decrease of CD11b+Ly6G+Ly6Clowcells in the spleen of WT animals, which was also not found in either HFD-fed CB2 knockouts or standard diet-fed WT and CB2 animals. Together with past report, these results suggest that CB2 receptors might have the double-sided regulatory role in context of the inflammation development, or more widely, immune system regulation. We propose that CB2 signaling is not always anti-inflammatory and could take pro-inflammatory role depending on the cause of the inflammation.
Conserved mycobacterial sRNA B11 regulates lipooligosaccharide synthesis at post-transcriptional level
Authors: Wang Chuan , Bei Cheng , Fan Yufeng , Liu Qingyun , Ding Yue , Takiff Howard E , Gao Qian
Published: June 2024

Extractable glycolipids of mycobacteria, such as lipooligosaccharides (LOS), play key roles in responding to environmental stress and altering the host immune response. However, although the biosynthesis of LOS is likely controlled at multiple levels to ensure proper composition of the cell wall, the key regulators are currently unknown. Here, we studied B11, a conserved mycobacterial sRNA, and found that it post-transcriptionally regulates LOS synthesis inMycobacteria marinum. Deletion of B11 alters the colony morphology and RNA sequencing combined with mass spectrometry identified several genes in the LOS synthesis locus that are regulated by B11. We found that B11 uses the cytosine-rich loops of its rho-independent transcriptional terminator to interact with guanine-tracks adjacent to the ribosome binding sites of its target genes, thereby impeding translation and promoting mRNA degradation by RNase E. These comprehensive functional studies of mycobacterial sRNA B11 demonstrate sRNA-based regulation of cell wall synthesis in mycobacteria.

Importance

Despite being identified for more than a decade, the functional characterization and regulatory mechanisms of mycobacterial sRNAs remain largely unexplored. We present here the most comprehensive functional study of mycobacterial sRNAs to date, employing convincible target screening using multifaceted experimental approaches and phenotype analysis. Our work reveals how synthesis of mycobacterial lipooligosaccharides (LOS), one of the crucial extractable glycolipids involved in environmental stress response and host immune modulation, is regulated at the post-transcriptional level by the conserved sRNA B11. Furthermore, our discovery of a highly conserved sRNA exhibiting distinct functions across mycobacterial species exemplifies divergent functional evolution among sRNAs.
Scalable Condition-relevant Cell Niche Analysis of Spatial Omics Data with Taichi
Authors: Cui Yan , Yuan Zhiyuan
Published: June 2024

Tissues are composed of heterogeneous cell niches, which can be investigated using spatial omics technologies. Large consortia have accumulated vast amounts of spatially resolved data, which typically assign slice-level condition labels without considering intra-slice heterogeneity, particularly differential cell niches that respond to certain perturbations. Here, we present Taichi, an efficient and scalable method for condition-relevant cell niche analysis that does not rely on pre-defined discrete spatial clustering. Taichi utilizes a scalable spatial co-embedding approach that effectively accounts for batch effects, incorporating advanced label refinement and graph heat diffusion techniques to explore condition-relevant cell niches across extensive multi-slice and multi-condition spatial omics datasets. Comprehensive benchmarks demonstrate Taichi’s ability to precisely identify condition-relevant niches under various levels of perturbations. We showcase Taichi’s effectiveness in accurately delineating major shifts in cell niches in a mouse model of diabetic kidney disease compared to a normal group, revealing disease-specific cell-cell interactions and spatial gene expression patterns. Furthermore, Taichi can identify key subtype-relevant niches between colorectal cancer patient groups with significantly different survival outcomes. Moreover, we demonstrate that Taichi can help discover more fine-grained clinical properties within the originally coarse-defined patient groups in large-scale tumor spatial atlases, reflecting intra-group heterogeneity obscured previously. Additionally, we combine Taichi and tensor decomposition to discover higher-order biomarkers relevant to the immunotherapy response of triple-negative breast cancer. Finally, we highlight Taichi’s speed and scalability by confirming its unique applicability in large-scale scenarios containing up to 16 million cells in ∼ 12 minutes. Taichi provides a powerful tool for mining disease-relevant spatially resolved insights in the era of big data in spatial biology.
ProTrek: Navigating the Protein Universe through Tri-Modal Contrastive Learning
Authors: Su Jin , Zhou Xibin , Zhang Xuting , Yuan Fajie
Published: June 2024

ProTrek redefines protein exploration by seamlessly fusing sequence, structure, and natural language function (SSF) into an advanced tri-modal language model. Through contrastive learning, ProTrek bridges the gap between protein data and human understanding, enabling lightning-fast searches across nine SSF pairwise modality combinations. Trained on vastly larger datasets, ProTrek demonstrates quantum leaps in performance: (1) Elevating protein sequence-function interconversion by 30-60 fold; (2) Surpassing current alignment tools (i.e., Foldseek and MMseqs2) in both speed (100-fold acceleration) and accuracy, identifying functionally similar proteins with diverse structures; and (3) Outperforming ESM-2 in 9 of 11 downstream prediction tasks, setting new benchmarks in protein intelligence. These results suggest that ProTrek will become a core tool for protein searching, understanding, and analysis.
Wounding triggers invasive progression in human basal cell carcinoma
Authors: Yerly Laura , Andreatta Massimo , Garnica Josep , Nardin Charlée , Domizio Jeremy Di , Aubin François , Gilliet Michel , Carmona Santiago J. , Kuonen François
Published: June 2024

The interconnection between wound healing and cancer has long been recognized, as epitomized by the expression “cancer is a wound that does not heal”. However, the impact of inducing a wound, such as through biopsy collection, on the progression of established tumors remains largely unknown. In this study, we apply single-cell spatial transcriptomics to characterize the heterogeneity of human basal cell carcinoma (BCC) and identify a wound response gene program as the most prominent feature of highly invasive BCC. To explore the causal relationship between wounding and cancer invasive progression, we perform a longitudinal experiment to compare human tumors at baseline and one week post-biopsy. Our results demonstrate that biopsy collection triggers, in proximity of the wound, the same transcriptional cancer cell state observed in highly invasive BCC. This cancer cell transcriptional switch is coupled with morphological changes and the transcriptional reprogramming of cancer-associated fibroblasts (CAFs). This study provides evidence that wounding triggers invasive progression of established human tumors and warrants further research on the potentially harmful effects of biopsies and wound-inducing treatments.
Motor cortex perineuronal net modulation improves motor function in a Parkinson’s disease mouse model
Authors: Benacom David , Chataing Camille , Prochiantz Alain , Di Nardo Ariel A.
Published: June 2024

The 6-OHDA mouse model recapitulates midbrain dopaminergic cell loss and associated motor deficits akin to those observed in Parkinson’s disease. Emerging evidence suggests that modulating interneurons in the primary motor cortex could offer a means to mitigate symptoms. In the cortex, perineuronal nets (PNNs), a specialized extracellular matrix structure generally present around fast-spiking parvalbumin interneurons, can modulate neural activity and circuit plasticity. We found that removing PNNs through unilateral or bilateral ChABC injection in the motor cortex temporarily altered motor behavior. Surprisingly, bilateral reduced motor cortex PNNs are observed two weeks after unilateral 6-OHDA midbrain lesions, whereas five weeks after lesion, PNNs return to control levels. Subsequent bilateral ChABC injections significantly improved motor function in 6-OHDA animals only when associated with motor stimulation involving enriched housing and daily motor training. Thus, PNN modulation in the motor cortex of a Parkinson’s disease model enables local circuits to adapt to the loss of dopaminergic inputs, resulting in improved motor behavior.
Aberrant TNF signaling in pancreatic lymph nodes of patients with Type 1 Diabetes
Authors: Abedi Maryam , Rai Priyadarshini , Zhou Yeqiao , Liu Chengyang , Johnson Isabelle , Chandra Aditi , Fasolino Maria , Rostami Susan , Kaestner Klaus H. , Naji Ali , Faryabi Robert B. , Vahedi Golnaz
Published: June 2024

The therapeutic landscape for Type 1 Diabetes (T1D) is rapidly changing as ongoing clinical trials aim to delay beta-cell loss by inhibiting proinflammatory cytokines. However, the precise timing and cellular contexts of cytokine dysregulation remains unknown. We generated the largest existing measurement of gene expression and chromatin accessibility in ∼1 million immune cells from the pancreatic lymph nodes and spleens of 34 T1D and non-diabetic organ donors. Our study revealed heightened gene activity of the tumor necrosis factor (TNF) pathway and subsequent chromatin remodeling in central memory CD4+T cells residing in the pancreatic lymph nodes of T1D and non-diabetic islet-autoantibody positive donors. These findings, validated in mice, offer a mechanism underlying the efficacy of TNF inhibitors, currently undergoing clinical trials to delay T1D onset.
cfDNA UniFlow: A unified preprocessing pipeline for cell-free DNA data from liquid biopsies
Authors: Röner Sebastian , Burkard Lea , Speicher Michael R. , Kircher Martin
Published: June 2024

Background

Cell-free DNA (cfDNA), a broadly applicable biomarker commonly sourced from urine or blood, is extensively used for research and diagnostic applications. In various settings, genetic and epigenetic information is derived from cfDNA. However, a unified framework for its processing is lacking, limiting the universal application of innovative analysis strategies and the joining of data sets.

Findings

Here, we describe cfDNA UniFlow, a unified, standardized, and ready-to-use workflow for processing cfDNA samples. The workflow is written in Snakemake and can be scaled from stand -alone computers to cluster environments. It includes methods for processing raw genome sequencing data as well as specialized approaches for correcting sequencing errors, filtering, and quality control. Sophisticated methods for detecting copy number alterations and estimating and correcting GC-related biases are readily incorporated. Furthermore, it includes methods for extracting, normalizing and visualizing coverage signals around user defined regions in case-control settings. Ultimately, all results and metrics are aggregated in a unified report, enabling easy access to a wide variety of information for further research and downstream analysis.

Conclusions

We provide an automated pipeline for processing cell-free DNA sampled from liquid biopsies, including a wide variety of additional functionalities like bias correction and signal extraction. With our focus on scalability and extensibility, we provide a foundation for future cfDNA research and faster clinical applications.

Issue Section

Technical Note

Availability and implementation

Source code and extensive documentation is available on our GitHub repository (https://github.com/kircherlab/cfDNA-UniFlow).
Efficient synthesis of 3D MR images for schizophrenia diagnosis classification with generative adversarial networks
Authors: King Sebastian , Hollenbenders Yasmin , Reichenbach Alexandra
Published: June 2024

Schizophrenia and other psychiatric disorders can greatly benefit from objective decision support in diagnosis and therapy. Machine learning approaches based on neuroimaging, e.g. magnetic resonance imaging (MRI), have the potential to serve this purpose. However, the medical data sets these algorithms can be trained on are often rather small, leading to overfit, and the resulting models can therewith not be transferred into a clinical setting. The generation of synthetic images from real data is a promising approach to overcome this shortcoming. Due to the small data set size and the size and complexity of medical images, i.e. their three-dimensional nature, those algorithms are challenged on several levels. We develop four generative adversarial network (GAN) architectures that tackle these challenges and evaluate them systematically with a data set of 193 MR images of schizophrenia patients and healthy controls. The best architecture, a GAN with spectral normalization regulation and an additional encoder (α-SN-GAN), is then extended with an auxiliary classifier into an ensemble of networks capable of generating distinct image sets for the two diagnostic categories. The synthetic images increase the accuracy of a diagnostic classifier from a baseline accuracy of around 61% to 79%. This novel end-to-end pipeline for schizophrenia diagnosis demonstrates a data and memory efficient approach to support clinical decision-making that can also be transferred to support other psychiatric disorders.