bluuebunny/crossref_metadata_2025 huggingface dataset:
Kinetics of skeletal muscle regeneration after mild and severe muscle damage induced by electrically‐evoked lengthening contractions
Authors: Bernard Clara , Jomard Charline , Chazaud Bénédicte , Gondin Julien
Published: August 2023

Post‐injury skeletal muscle regeneration requires interactions between myogenic and non‐myogenic cells. Our knowledge on the regeneration process is mainly based on models using toxic, chemical, or physical (e.g., based on either muscle freezing or crushing) injury. Strikingly, the time course and magnitude of changes in the number of cells involved in muscle regeneration have been poorly described in relation to mild and severe muscle damage induced by electrically‐evoked lengthening contractions. We investigated for the first time the kinetics and magnitude of changes in mononuclear cells in relation to the extent of muscle damage. Mild and severe injury were induced in vivo in the mouse gastrocnemius muscle by 1 and 30 electrically‐evoked lengthening contractions, respectively. Several days after muscle damage, functional analysis of maximal torque production and histological investigations were performed to assess the related cellular changes. Torque recovery was faster after mild injury than after severe muscle damage. More necrotic and regenerating myofibers were observed after severe muscle damage as compared with mild injury, illustrating an association between functional and histological alterations. The kinetics of changes in muscle stem cells (total, proliferating, and differentiating), endothelial cells, fibro‐adipogenic progenitors (FAPs), and macrophages in the regenerating muscle was similar in mild and severe models. However, the magnitude of changes in the number of differentiating muscle stem cells, hematopoietic cells, among which macrophages, and FAPs was higher in severe muscle damage. Collectively, our results show that the amount of myogenic and non‐myogenic cells varies according to the extent of skeletal muscle injury to ensure efficient skeletal muscle regeneration while the kinetics of changes is independent of muscle tissue alterations. The possibility to experimentally modulate the extent of muscle damage will be useful to further investigate the cellular and molecular events involved in muscle regeneration.
Neutrophil extracellular traps facilitate sympathetic hyperactivity by polarizing microglia toward M1 phenotype after traumatic brain injury
Authors: Qu Xiaolin , Hou Xiaoxiang , Zhu Kaixin , Chen Wen , Chen Kun , Sang Xianzheng , Wang Chenqing , Zhang Yelei , Xu Haoxiang , Wang Junyu , Hou Qibo , Lv Liquan , Hou Lijun , Zhang Danfeng
Published: August 2023

Traumatic brain injury (TBI), particularly diffuse axonal injury (DAI), often results in sympathetic hyperactivity, which can exacerbate the prognosis of TBI patients. A key component of this process is the role of neutrophils in causing neuroinflammation after TBI by forming neutrophil extracellular traps (NETs), but the connection between NETs and sympathetic excitation following TBI remains unclear. Utilizing a DAI rat model, the current investigation examined the role of NETs and the HMGB1/JNK/AP1 signaling pathway in this process. The findings revealed that sympathetic excitability intensifies and peaks 3 days post‐injury, a pattern mirrored by the activation of microglia, and the escalated NETs and HMGB1 levels. Subsequent in vitro exploration validated that HMGB1 fosters microglial activation via the JNK/AP1 pathway. Moreover, in vivo experimentation revealed that the application of anti‐HMGB1 and AP1 inhibitors can mitigate microglial M1 polarization post‐DAI, effectively curtailing sympathetic hyperactivity. Therefore, this research elucidates that post‐TBI, NETs within the PVN may precipitate sympathetic hyperactivity by stimulating M1 microglial polarization through the HMGB1/JNK/AP1 pathway.
Perinatal Mortality Despite Prenatal Diagnosis of Vasa Previa
Authors: Heyborne Kent
Published: August 2023

OBJECTIVE:

To determine the causes and potential preventability of perinatal deaths in prenatally identified cases of vasa previa.

DATA SOURCES:

Reports of prenatally identified cases of vasa previa published in the English language literature since 2000 were identified in Medline and ClinicalTrials.gov with the search terms “vasa previa,” “abnormal cord insertion,” “velamentous cord,” “marginal cord,” “bilobed placenta,” and “succenturiate lobe.”

METHODS OF STUDY SELECTION:

All cases from the above search with an antenatally diagnosed vasa previa present at delivery in singleton or twin gestations with perinatal mortality information were included.

TABULATION, INTEGRATION, AND RESULTS:

Cases meeting inclusion criteria were manually abstracted, and multiple antenatal, intrapartum, and outcome variables were recorded. Deaths and cases requiring neonatal transfusion were analyzed in relation to plurality, routine hospitalization, and cervical length monitoring. A total of 1,109 prenatally diagnosed cases (1,000 singletons, 109 twins) were identified with a perinatal mortality rate attributable to vasa previa of 1.1% (95% CI 0.6–1.9%). All perinatal deaths occurred with unscheduled deliveries. The perinatal mortality rate in twin pregnancies was markedly higher than that in singleton pregnancies (9.2% vs 0.2%, P<.001), accounting for 80% of overall mortality despite encompassing only 9.8% of births. Compared with individuals with singleton pregnancies, those with twin pregnancies are more likely to undergo unscheduled delivery (56.4% vs 35.1%, P=.01) despite delivering 2 weeks earlier (33.2 weeks vs 35.1 weeks, P=.006). An institutional policy of routine hospitalization is associated with a reduced need for neonatal transfusion (0.9% vs 6.0%, P<.001) and a reduction in the perinatal mortality rate in twin pregnancies (0% vs 25%, P=.002) but not in singleton pregnancies (0% vs 0.5%, P=.31).

CONCLUSION:

Routine hospitalization and earlier delivery of twins may result in a reduction in the perinatal mortality rate. A smaller benefit from routine admission of individuals with singleton pregnancies cannot be excluded. There is currently insufficient evidence to recommend the routine use of cervical length measurements to guide clinical management.
Association of Clinical Trial Participation With Improved Overall Survival for Recurrent, Platinum-Resistant Ovarian Cancer
Authors: Morton Molly , Yao Meng , Chalif Julia , Lampert Erika J. , Chau Danielle , Rose Peter G. , Debernardo Robert , Michener Chad M. , Vargas Roberto , Chambers Laura M.
Published: August 2023

OBJECTIVE:

To investigate whether clinical trial participation is associated with overall survival in patients with platinum-resistant ovarian cancer.

METHODS:

An IRB-approved, retrospective, single-institution cohort study was performed in patients with platinum-resistant ovarian cancer from January 1, 2009, to December 31, 2017. Platinum resistance was defined as progression within 6 months after completion of platinum chemotherapy. Patients were divided into two cohorts: 1) clinical trial participants for platinum-resistant ovarian cancer or 2) standard of care. The association of trial participation with overall survival from the date of platinum resistance was assessed with univariate and multivariable models.

RESULTS:

Of 305 eligible patients with recurrent platinum-resistant ovarian cancer, 46 (15.1%) were clinical trial participants. There were no significant differences in age (61.2 years vs 63.3 years, P=.21), body mass index (27.5 vs 27.6, P=.90), race (P=.61), medical comorbidities (P>.05), or performance status (P=.07) for clinical trial participants compared with those receiving standard of care. The majority underwent primary cytoreduction (76.1% vs 69.1%, P=.34) with no differences in residual disease (P=.43) for clinical trial participants compared with those receiving standard of care. There was no difference in poly-ADP-ribose polymerase inhibitor (21.7% vs 15.1%, P=.26) or bevacizumab (22.2% vs 32.1%, P=.31) use for clinical trial participants compared with those receiving standard of care. On multivariable analysis controlling for comorbidities, stage, and germline mutational status, clinical trial participation was associated with significantly improved overall survival from the date of platinum resistance compared with standard of care (13.8 months vs 10.5 months, adjusted hazard ratio 1.46, 95% CI 1.04–2.05, P=.028).

CONCLUSIONS:

In this retrospective cohort of patients with platinum-resistant ovarian cancer, clinical trial participation was associated with improved overall survival compared with standard of care therapies. Availability and participation in clinical trials should be prioritized in patients with recurrent, platinum-resistant ovarian cancer.
Risks of Uterine Perforation and Expulsion Associated With Intrauterine Devices
Authors: Fassett Michael J. , Reed Susan D. , Rothman Kenneth J. , Pisa Federica , Schoendorf Juliane , Wahdan Yesmean , Peipert Jeffrey F. , Gatz Jennifer , Ritchey Mary E. , Armstrong Mary Anne , Raine-Bennett Tina , Postlethwaite Debbie , Getahun Darios , Shi Jiaxiao M. , Xie Fagen , Chiu Vicki Y. , Im Theresa M. , Takhar Harpreet S. , Wang Jinyi , Anthony Mary S.
Published: August 2023

OBJECTIVE:

The APEX-IUD (Association of Perforation and Expulsion of Intrauterine Devices) study evaluated the association of postpartum timing of intrauterine device (IUD) insertion, breastfeeding, heavy menstrual bleeding, and IUD type (levonorgestrel-releasing vs copper) with risks of uterine perforation and IUD expulsion in usual clinical practice. We summarize the clinically important findings to inform counseling and shared decision making.

METHODS:

APEX-IUD was a real-world (using U.S. health care data) retrospective cohort study of individuals aged 50 years and younger with IUD insertions between 2001 and 2018 and with electronic health record data. Cumulative incidences of uterine perforation and IUD expulsion were calculated. Adjusted hazard ratios (aHRs) and 95% CIs were estimated from proportional hazards models with control of confounding.

RESULTS:

Among the study population of 326,658, absolute risk of uterine perforation was low overall (cumulative incidence, 0.21% [95% CI 0.19–0.23%] at 1 year and 0.61% [95% CI 0.56–0.66% at 5 years]) but was elevated for IUDs inserted during time intervals within 1 year postpartum, particularly among those between 4 days and 6 weeks postpartum (aHR 6.71, 95% CI 4.80–9.38), relative to nonpostpartum insertions. Among postpartum insertions, IUD expulsion risk was greatest for insertions in the immediate postpartum period (0–3 days after delivery) compared with nonpostpartum (aHR 5.34, 95% CI 4.47–6.39). Postpartum individuals who were breastfeeding had a slightly elevated risk of perforation and lowered risk of expulsion than those not breastfeeding. Among nonpostpartum individuals, those with a heavy menstrual bleeding diagnosis were at greater risk of expulsion than those without (aHR 2.84, 95% CI 2.66–3.03); heavy menstrual bleeding also was associated with a slightly elevated perforation risk. There was a slightly elevated perforation risk and slightly lower expulsion risk associated with levonorgestrel-releasing IUDs compared with copper IUDs.

CONCLUSION:

Absolute risk of adverse outcomes with IUD insertion is low. Clinicians should be aware of the differences in risks of uterine perforation and expulsion associated with IUD insertion during specific postpartum time periods and with a heavy menstrual bleeding diagnosis. This information should be incorporated into counseling and decision making for patients considering IUD insertion.

FUNDING SOURCE:

Bayer AG.

CLINICAL TRIAL REGISTRATION:

EU PAS register, EUPAS33461.
Comparison of Antiretroviral Therapies in Pregnant Women Living With Human Immunodeficiency Virus and Hepatitis B Virus
Authors: Bhattacharya Debika , Tierney Camlin , Butler Kevin , Kiweewa Flavia Matovu , Moodley Dhayendre , Govender Vani , Vhembo Tichaona , Mohtashemi Neaka , Ship Hannah , Dula Dingase , George Kathy , Chaktoura Nahida , Fowler Mary Glenn , Peters Marion G. , Currier Judith S.
Published: August 2023

OBJECTIVE:

To describe the anti–hepatitis B virus (HBV) efficacy, HBeAg serologic changes, HBV perinatal transmission, and safety in pregnant women who are living with human immunodeficiency virus (HIV) and HBV co-infection who were randomized to various antiretroviral therapy (ART) regimens.

METHODS:

The PROMISE (Promoting Maternal and Infant Survival Everywhere) trial was a multicenter randomized trial for ART-naive pregnant women with HIV infection. Women with HIV and HBV co-infection at 14 or more weeks of gestation were randomized to one of three ART arms: one without HBV treatment (group 1) and two HBV treatment arms with single (group 2) or dual anti-HBV activity (group 3). The primary HBV outcome was HBV viral load antepartum change from baseline (enrollment) to 8 weeks; safety assessments included alanine aminotransferase (ALT) level, aspartate aminotransferase (AST) level, and anemia (hemoglobin less than 10 g/dL). Primary comparison was for the HBV-active treatment arms. Pairwise comparisons applied t test and the Fisher exact tests.

RESULTS:

Of 3,543 women, 3.9% were HBsAg-positive; 42 were randomized to group 1, 48 to group 2, and 48 to group 3. Median gestational age at enrollment was 27 weeks. Among HBV-viremic women, mean antepartum HBV viral load change at week 8 was −0.26 log10 international units/mL in group 1, −1.86 in group 2, and −1.89 in group 3. In those who were HBeAg-positive, HBeAg loss occurred in 44.4% at delivery. Two perinatal HBV transmissions occurred in group 2. During the antepartum period, one woman (2.4%) in group 1 had grade 3 or 4 ALT or AST elevations, two women (4.2%) in group 2, and three women (6.3%) in group 3.

CONCLUSION:

Over a short period of time, HBV DNA suppression was not different with one or two HBV-active agents. HbeAg loss occurred in a substantial proportion of participants. Perinatal transmission of HBV infection was low. Hepatitis B virus–active ART was well-tolerated in pregnancy, with few grade 3 or 4 ALT or AST elevations.

CLINICAL TRIAL REGISTRATION:

ClinicalTrials.gov, NCT01061151.
Abnormal Postoperative PROMIS Scores are Associated with Patient Satisfaction in Adult Spinal Deformity and Degenerative Spine Patients
Authors: Covarrubias Oscar , Andrade Nicholas S , Mo Kevin C , Dhanjani Suraj , Olson Jarod , Musharbash Farah N , Sachdev Rahul , Kebaish Khaled M , Skolasky Richard L , Neuman Brian J
Published: August 2023

Study Design.

Retrospective review

Objectives.

To evaluate 1) patient satisfaction after adult spine surgery; 2) associations between number of abnormal PROMIS domain scores and postoperative satisfaction; and 3) associations between normalization of a patient’s worst preoperative PROMIS domain score and postoperative satisfaction.

Summary of Background Data.

Although “legacy” patient-reported outcome measures correlate with patient satisfaction after adult spine surgery, it is unclear whether PROMIS scores do.

Methods.

We included 1119 patients treated operatively for degenerative spine disease (DSD) or adult spinal deformity (ASD) from 2014–2019 at our tertiary hospital who completed questionnaires preoperatively and at ≥1 postoperative timepoints up to 2 years. Postoperative satisfaction was measured in ASD patients using items 21 and 22 from the SRS 22-revised questionnaire and in DSD patients using the NASS Patient Satisfaction Index. “Worst” preoperative PROMIS domain was that with the greatest clinically negative deviation from the mean. “Normalization” was a postoperative score within 1 standard deviation of the general population mean. Multivariate logistic regression identified factors associated with satisfaction.

Results.

Satisfaction was reported by 88% of DSD and 86% of ASD patients at initial postoperative follow-up; this proportion did not change during the first year after surgery. We observed an inverse relationship between postoperative satisfaction and number of abnormal PROMIS domains at all postoperative timepoints beyond 6 weeks. Only among ASD patients was normalization of the worst preoperative PROMIS domain associated with greater odds of satisfaction at all timepoints up to 1 year.

Conclusion.

The proportion of DSD and ASD patients satisfied postoperatively did not change from 6 weeks to 1 year. Normalizing the worst preoperative PROMIS domain and minimizing the number of abnormal postoperative PROMIS scores may reduce the number of dissatisfied patients. PROMIS data can guide perioperative patient management to improve satisfaction.

Level of Evidence.

3
Innovative Approach to Unicondylar Proximal Phalangeal Fracture Fixation: Combining Antegrade Intramedullary Pinning With Flexion Proximal Interphalangeal Joint Transfixation
Authors: Kuo Hsueh-Min , Huang Hui-Kuang , Yin Cheng-Yu , Huang Yi-Chao , Wang Jung-Pan
Published: August 2023

Various surgical techniques have been described for the fixation of displaced unicondylar fractures of the proximal phalanx, with K-wire and interfragmentary screws being the most commonly used. Although open reduction with joint exposure can provide direct visualization and allow for anatomic reduction, its potential drawbacks, such as joint stiffness and loss of range of motion, are of significant concern. We introduced a novel fixation technique for displaced unicondylar fractures of the proximal phalanx using antegrade intramedullary pinning and transfixation of the proximal interphalangeal joint, which is simple, effective, and does not require open reduction.
Single-cell multiomic understanding of HIV-1 reservoir at epigenetic, transcriptional, and protein levels
Authors: Wong Michelle , Wei Yulong , Ho Ya-Chi
Published: August 2023

Purpose of review

The success of HIV-1 eradication strategies relies on in-depth understanding of HIV-1-infected cells. However, HIV-1-infected cells are extremely heterogeneous and rare. Single-cell multiomic approaches resolve the heterogeneity and rarity of HIV-1-infected cells.

Recent findings

Advancement in single-cell multiomic approaches enabled HIV-1 reservoir profiling across the epigenetic (ATAC-seq), transcriptional (RNA-seq), and protein levels (CITE-seq). Using HIV-1 RNA as a surrogate, ECCITE-seq identified enrichment of HIV-1-infected cells in clonally expanded cytotoxic CD4+ T cells. Using HIV-1 DNA PCR-activated microfluidic sorting, FIND-seq captured the bulk transcriptome of HIV-1 DNA+ cells. Using targeted HIV-1 DNA amplification, PheP-seq identified surface protein expression of intact versus defective HIV-1-infected cells. Using ATAC-seq to identify HIV-1 DNA, ASAP-seq captured transcription factor activity and surface protein expression of HIV-1 DNA+ cells. Combining HIV-1 mapping by ATAC-seq and HIV-1 RNA mapping by RNA-seq, DOGMA-seq captured the epigenetic, transcriptional, and surface protein expression of latent and transcriptionally active HIV-1-infected cells. To identify reproducible biological insights and authentic HIV-1-infected cells and avoid false-positive discovery of artifacts, we reviewed current practices of single-cell multiomic experimental design and bioinformatic analysis.

Single-cell multiomic approaches may identify innovative mechanisms of HIV-1 persistence, nominate therapeutic strategies, and accelerate discoveries.
Serratus Anterior-rib Composite Flap Partial Thumb Reconstruction
Authors: Xu Kyle Y. , Qureshi Hassan A. , Tadisina Kashyap Komarraju , Frojo Gianfranco , Kraemer Bruce A.
Published: August 2023

The serratus anterior-rib composite flap is a well described and versatile flap used for reconstruction in a variety of anatomical regions. However, reconstruction of a thumb defect using this flap has not been well described since first mentioned in the literature by the Buncke et al group 20 years ago. The authors describe the use of this technique for thumb reconstruction in a complex defect from a gunshot wound.
Usefulness of Harmonic ACE+7 Scalpel in Breast Reconstruction with Extended Latissimus Dorsi Flap: An Open-label Single Institution Pilot Study
Authors: Takaya Kento , Baba Miho , Kuranami Masaru , Shido Hirokazu , Asou Toru , Kishi Kazuo
Published: August 2023

Background:

The extended latissimus dorsi (ELD) flap is a safe and aesthetically acceptable method to reconstruct small to medium-sized breasts. However, the long time required for flap elevation and intraoperative bleeding contributes to various postoperative complications. We investigated the use of alternative devices, such as the Harmonic ACE+7, which has a long arm that can help simultaneously detach and seal tissues to prevent such complications.

Methods:

We compared 27 patients who underwent breast reconstruction with the ELD flap using the Harmonic ACE +7 scalpel, and 28 patients who underwent breast reconstruction using an electrocautery scalpel, between May 2019 and March 2022. Data on patient demographics, surgery, and postoperative complications were collected. Surgical outcomes were compared between electrocautery (EC) and Harmonic ACE+7 (HA) groups.

Results:

The median age of the patients was 50.2 years. The patient demographics between the groups did not show significant differences. Flap necrosis and hematomas did not occur, and seroma was the major postoperative complication (65.7% in the EC group and 70% in the HA group). The time required for flap elevation was significantly shorter in the HA group than in the EC group (286.0 minutes and 179.0 minutes, respectively). Blood loss reduced significantly in the HA and EC groups (138.5 mL and 78.2 mL, respectively). Moreover, decreased drainage was observed for the breast area. There were no significant differences in other end points.

Conclusion:

In breast reconstruction with ELD flaps, using the Harmonic ACE+7 can help reduce the rate of seroma, operative time, and intraoperative bleeding without further disadvantages.
Living donor liver transplantation can address disparities in transplant access for patients with primary sclerosing cholangitis
Authors: Onofrio Fernanda , Zheng Katina , Xu Cherry , Chen Shiyi , Xu Wei , Vyas Mary , Bingham Katie , Patel Keyur , Lilly Leslie , Cattral Mark , Selzner Nazia , Jaeckel Elmar , Tsien Cynthia , Gulamhusein Aliya , Hirschfield Gideon M. , Bhat Mamatha
Published: August 2023

Background:

Liver transplantation (LT) is frequently lifesaving for people living with primary sclerosing cholangitis (PSC). However, patients are waitlisted for LT according to the model for end-stage liver disease-sodium (MELD-Na) score, which may not accurately reflect the burden of living with PSC. We sought to describe and analyze the clinical trajectory for patients with PSC referred for LT, in a mixed deceased donor/living donor transplant program.

Methods:

This was a retrospective cohort study from November 2012 to December 2019, including all patients with PSC referred for assessment at the University Health Network Liver Transplant Clinic. Patients who required multiorgan transplant or retransplantation were excluded. Liver symptoms, hepatobiliary malignancy, MELD-Na progression, and death were abstracted from chart review. Competing risk analysis was used for timing of LT, transplant type, and death.

Results:

Of 172 PSC patients assessed, 84% (n = 144) were listed of whom 74% were transplanted. Mean age was 47.6 years, and 66% were male. Overall mortality was 18.2% at 2 years. During the follow-up, 16% (n = 23) were removed from the waitlist for infection, clinical deterioration, liver-related mortality or new cancer; 3 had clinical improvement. At listing, 82% (n = 118) had a potential living donor (pLD). Patients with pLD had significantly lower waitlist and liver-related waitlist mortality (HR 0.20, p<0.001 and HR 0.17, p<0.001, respectively), and higher rates of transplantation (HR 1.83, p = 0.05). Exception points were granted to 13/172 (7.5%) patients.

Conclusions:

In a high-volume North American LT center, most patients with PSC assessed for transplant were listed and subsequently transplanted. However, this was a consequence of patients engaging in living donor transplantation. Our findings support the concern from patients with PSC that MELD-Na allocation does not adequately address their needs.
Thyroid hormone action and liver disease, a complex interplay
Authors: Marino Luigi , Kim Adam , Ni Bin , Celi Francesco S.
Published: August 2023

Thyroid hormone action is involved in virtually all physiological processes. It is well known that the liver and thyroid are intimately linked, with thyroid hormone playing important roles in de novo lipogenesis, beta-oxidation (fatty acid oxidation), cholesterol metabolism, and carbohydrate metabolism. Clinical and mechanistic research studies have shown that thyroid hormone can be involved in chronic liver diseases, including alcohol-associated or NAFLD and HCC. Thyroid hormone action and synthetic thyroid hormone analogs can exert beneficial actions in terms of lowering lipids, preventing chronic liver disease and as liver anticancer agents. More recently, preclinical and clinical studies have indicated that some analogs of thyroid hormone could also play a role in the treatment of liver disease. These synthetic molecules, thyromimetics, can modulate lipid metabolism, particularly in NAFLD/NASH. In this review, we first summarize the thyroid hormone signaling axis in the context of liver biology, then we describe the changes in thyroid hormone signaling in liver disease and how liver diseases affect the thyroid hormone homeostasis, and finally we discuss the use of thyroid hormone-analog for the treatment of liver disease.
OCTA Biomarkers and Microperimetry Features in Behçet's Uveitis
Authors: Ferreira Bruno F. A. , Higashi Alex H. , Prado Leandro L. , Gonçalves Célio R. , Haddad Maria A. O. , Zacharias Leandro C. , Hirata Carlos E. , Yamamoto Joyce H.
Published: August 2023

Purpose:

To evaluate the parafoveal macular microvasculature and the macular function in patients with retinal vasculitis associated with Behçet's uveitis (BU).

Methods:

In 14 patients with inactive BU and 26 control individuals (13 with nonocular Behçet's syndrome and 13 healthy subjects), we analyzed the retinal nerve fiber layer, ganglion cell layer (GCL), full retinal thickness (FRT), foveal avascular zone area and sectorial parafoveal vessel density in the superficial vascular plexus, intermediate capillary plexus, and deep capillary plexus (DCP) using Spectralis optical coherence tomography (OCT) 2 and OCT angiography (OCTA). Macular sensitivity was analyzed using an MP-3 microperimeter.

Results:

Eighteen eyes (78%) had a best-corrected visual acuity (BCVA) > 20/25. Significant differences were found in BU in comparison to the controls on the OCT and OCTA: 14.8%, 22.4%, and 14.9% GCL thinning in the global, nasal, and inferior sectors, respectively; 6%, 13.2%, and 7.5% FRT thinning in the superior, nasal, and inferior sectors; and 16.8%, 14.9%, 23.6%, 15.8%, and 12.6% mean DCP density reduction in the global, superior, nasal, inferior, and temporal sectors. Microperimetry data demonstrated significant mean reductions of 21% and 23.6% in central and average macular sensitivities, and 28.8%, 40.4%, 27.7%, and 24.2% in the superior, nasal, inferior, and temporal sectors, respectively. Outer plexiform layer elevations were observed in BU (69.6%).

Conclusions:

BU presented structural and functional macular damage despite good BCVA, mainly affecting the nasal sector and the DCP. On OCT and OCTA, quantitative and qualitative changes can be valuable biomarkers of ocular involvement in BS.
Characteristics of surgically induced astigmatism after standardized microincisional cataract surgery with a superior limbal incision
Authors: Wendelstein Jascha , Casazza Marina , Riaz Kamran M. , Fischinger Isaak , Fuchs Barbara , Bolz Matthias , Seiler Theo G. , Kohnen Thomas , Langenbucher Achim
Published: August 2023

Purpose:

To determine (1) if measurements of surgically induced astigmatism (SIA) as measured by keratometry (K) and total keratometry (TK) differ (2) if SIA affects the magnitude and/or meridian of keratometric astigmatism (3) if SIA evolves over time.

Setting:

Tertiary care center.

Design:

Retrospective data analysis.

Methods:

A swept-source optical coherence tomography biometry dataset (IOLMaster700) consisting of 498 eyes (327 patients) from a tertiary care center was analyzed. For all eyes preoperative and postoperative biometric measurements at 1-month, 3-month, and 6-months postoperative visits were considered for vector analysis of SIAK and SIATK.

Results:

Centroids in right and left eyes were 0.26 diopters (D) @5 degrees/0.31 D @1 degree for SIAK and 0.27 D @4 degrees/0.34 D @1 degree for SIATK. Centroids for difference vectors K-TK in right and left eyes were 0.02 D @ 176 degrees/0.03 D @6 degrees. The mean SIA magnitudes in right and left eyes were 0.48 ± 0.41 D and 0.50 ± 0.37 D for SIAK and 0.53 ± 0.42 D and 0.54 ± 0.40 D for SIATK. In eyes with ATR astigmatism, an increase in postoperative astigmatism magnitude was more common than a decrease. More than 30% of eyes showed changes in the meridian of more than 15 degrees.

Conclusions:

Overall, we observed differences in K- and TK-derived SIA, and changes in SIA magnitude over time. For postsurgical interventions, postoperative astigmatism meridian values should be measured to base treatments. Astigmatism magnitude showed a tendency to decrease for steep-meridian incisions and to increase in flat-meridian incisions.
Quantitative somatosensory testing of the abdomen: establishing initial reference values across developmental age and biological sex
Authors: Sieberg Christine B. , Lunde Claire E. , Shafrir Amy L. , Meints Samantha M. , Madraswalla Mehnaz , Huntley Devon , Olsen Hannah , Wong Cindy , DiVasta Amy D. , Missmer Stacey A. , Sethna Navil
Published: August 2023

Abdominal pain is a common symptom of several debilitating conditions (eg, inflammatory bowel disease, irritable bowel syndrome, and endometriosis) and affects individuals throughout their lifespan. Quantitative sensory testing (QST) reference values exist for many body sites but not the abdomen. Using a QST battery adapted from the German Research Network on Neuropathic Pain, we collected QST data on the upper and lower abdomen in 181 pain-free participants, ages 12 to 50 years, to establish reference values by age and biological sex. The normative values are presented as medians for each QST measure by sex (male, n = 63; female, n = 118) and across 3 age categories (adolescents: 12-19 years, n = 48; young adults: 20-30 years, n = 87; and adults: 31-50 years, n = 46). Evaluating the sensory functioning of the abdomen and characterizing ranges of QST measures is an essential first step in understanding and monitoring the clinical course of sensory abnormalities in patients with underlying diseases affecting the abdomen and pelvis. The impact of age and development on sensory functioning is necessary, given age-related changes in pain perception and modulation.
Residual risk of hepatocellular carcinoma development for chronic hepatitis C patients treated by all oral direct-acting antivirals with sustained virological response
Authors: Luan Chih-Hsuan , Su Pin-Shuo , Chu Chi-Jen , Lin Chung-Chi , Su Chien-Wei , Lee Shou-Dong , Wang Yuan-Jen , Lee Fa-Yauh , Huang Yi-Hsiang , Hou Ming-Chih
Published: August 2023

Background:

The treatment of chronic hepatitis C (CHC) infection underwent a significant transformation with the introduction of all-oral direct-acting anti-virals (DAAs). These medications offered a high success rate in treatment, shorter duration, good tolerability, and expanded treatment options. However, a residual risk of hepatocellular carcinoma (HCC) development remained for a few patients even after achieving sustained virological response (SVR). To date, there is a lack of real-world data on evaluating risk factors associated with de novo HCC in CHC patients post-SVR, particularly in Taiwan.

Methods:

Between January 2017 and December 2019, a total of 671 consecutive CHC patients who achieved SVR after receiving DAAs were included for analysis. Patients with a history of HCC or liver transplantation prior to DAAs, a short follow-up period (<1 year), or treatment failure with DAAs were excluded. The primary outcome was the development of HCC following the initiation of DAAs. Variables associated with the primary outcome were assessed using multivariate Cox proportional hazards models.

Results:

The mean age of the enrolled patients was 65.1 ± 12.8 years, with 39.6% of them being male. Among the patients, 30.6% had advanced (F3-4) fibrosis, and the median follow-up period was 2.90 years. The cumulative incidence of HCC in CHC patients post-SVR12 was 1.6% at 1 year, 4.4% at 2 years, 4.8% at 3 years, 5.3% at 4 years, and 6.1% at 4.8 years, respectively. Variables independently associated with de novo HCC were advanced liver fibrosis (hazard ratio [HR] = 6.745; 95% CI = 1.960-23.218; p = 0.002), end-of-treatment 12 weeks (EOT12) alpha-fetoprotein (AFP) >7 ng/mL (HR = 3.059; 95% CI = 1.215-7.669; p = 0.018), EOT12 albumin-bilirubin (ALBI) grade ≥ 2 (HR = 2.664; 95% CI = 1.158-6.128; p = 0.021), and body mass index (BMI) ≥ 25 kg/m2 (HR = 2.214; 95% CI = 1.011-4.852; p = 0.047).

Conclusion:

Despite achieving viral clearance with DAAs, CHC patients still face a residual risk of de novo HCC. Establishing a risk stratification model based on independent variables could facilitate the prediction of future HCC development and enhance screening strategies.
Is Fasciotomy Associated With Increased Mortality in Extracorporeal Cardiopulmonary Resuscitation?
Authors: Shu Henry T. , Cho Sung-Min , Harris Andrew B. , Jami Meghana , Shou Benjamin L. , Griffee Matthew J. , Zaaqoq Akram M. , Wilcox Christopher J. , Anders Marc , Rycus Peter , Whitman Glenn , Kim Bo Soo , Shafiq Babar ,   on behalf of the Hopkins Education, Research, and Advancement in Life Support Devices (HERALD) Group
Published: August 2023

Our primary objective was to identify if fasciotomy was associated with increased mortality in patients who developed acute compartment syndrome (ACS) on extracorporeal cardiopulmonary resuscitation (ECPR). Additionally, we sought to identify any additional risk factors for mortality in these patients and report the amputation-free survival following fasciotomy. We retrospectively reviewed adult ECPR patients from the Extracorporeal Life Support Organization registry who were diagnosed with ACS between 2013 and 2021. Of 764 ECPR patients with limb complications, 127 patients (17%) with ACS were identified, of which 78 (63%) had fasciotomies, and 14 (11%) had amputations. Fasciotomy was associated with a 23% rate of amputation-free survival. There were no significant differences in demographics or baseline laboratory values between those with and without fasciotomy. Overall, 88 of 127 (69%) patients with ACS died. With or without fasciotomy, the mortality of ACS patients was similar, 68% vs. 71%. Multivariable logistic regression demonstrated that body mass index (BMI; adjusted odds ratio [aOR] = 1.22, 95% confidence interval [CI] = 1.01–1.48) and 24 hour mean blood pressure (BP; aOR = 0.93, 95% CI = 0.88–0.99) were independently associated with mortality. Fasciotomy was not an independent risk factor for mortality (aOR = 0.24, 95% CI = 0.03–1.88). The results of this study may help guide surgical decision-making for patients who develop ACS after ECPR. However, the retrospective nature of this study does not preclude selection bias in patients who have received fasciotomy. Thus, prospective studies are necessary to confirm these findings.
Neither Words nor Images: Health Departments' and Hospitals' Use of Twitter During COVID-19 Had Limited Racial Representation and Content on Disparities Decreased Over Time
Authors: Sheth Poorva , Thompson Chloe , Bhavsar Avi , Smith Allie , Rozier Michael
Published: August 2023

Objective:

To determine the degree to which hospitals and state health departments used written content or visual representation on social media to draw attention to racial disparities during the COVID-19 pandemic.

Study Design:

A retrospective analysis, using Twitter content (words and images) between May-June 2020 and May-June 2021 from organizations in the 5 states with the largest documented racial disparities in COVID-19–related mortality.

Main Outcomes:

All tweets and retweets (n = 6790) were coded along several lines. For May-June 2020 and May-June 2021, posts were coded as pandemic related (yes/no) and disparities related (yes/no). Open-coding methods categorized pandemic-related content into content areas, including COVID-19 education, hospital or public policy, and addressing misinformation. After self-identifying their own race/ethnicity, survey respondents (n = 100) coded pandemic-related Twitter images (n = 198) as including individuals of a similar race/ethnicity (yes/no).

Results:

In May-June 2020, health departments posted more pandemic-related content than hospitals (μ = 204 and 71 tweets, respectively; P = .03), including more about health disparities (μ = 14.3% and 2.11% of tweets, respectively; P = .03). Between May-June 2020 and May-June 2021, content addressing health disparities decreased for both groups (47% decrease for health departments and 69% decrease for hospitals). Black respondents were more likely to feel represented in images from health departments than in those from hospitals (44.3% and 23.7% of images, respectively; P = .05). Both hospitals and health departments were more likely to use images where White respondents felt represented (hospitals = 76.1% of images; health departments = 59.7%) than images where respondents from racial/ethnic minorities felt represented (hospitals = 19.3% of images; health departments = 21.4%) (P ≤ .001 for hospitals; P = .004 for health departments).

Conclusions:

Health education ideally comes in a variety of ways. Hospitals used social media for this purpose less than health departments, and neither group increased such content during the COVID-19 pandemic even as evidence of racial disparities grew.
HIV and urethritis: Time required for antiretroviral therapy to suppress HIV in semen
Authors: Matoga Mitch , Chen Jane S. , Massa Cecilia , Thengolose Isaac , Tegha Gerald , Ndalama Beatrice , Bonongwe Naomi , Mathiya Esther , Jere Edward , Banda Gabriel , Khan Shiraz , Loftis Amy J. , Kashuba Angela , Cottrell Mackenzie L. , Schauer Amanda P. , Van Horne Brian , Tompkins Lauren A. , Lancaster Kathryn E. , Miller William C. , Eron Joseph E. , Hoffman Irving F. , Cohen Myron S.
Published: August 2023

Objectives:

To examine the time required to suppress HIV in the genital tract with antiretroviral therapy (ART) in men with urethritis.

Design:

An observational cohort study.

Methods:

Men with HIV and urethritis not on ART were enrolled at an STI clinic in Malawi and offered to initiate ART. Blood and semen samples were collected pre-treatment and at 1, 2, 4, 8, 12 and 24 weeks post-urethritis treatment. Median viral loads (VL) were calculated by ART initiation groups: ‘within 1 week’, ‘between 1–4 weeks’ and ‘no ART before 4 weeks’, based on the men's choice about whether or not to initiate ART. The presence of ART at each visit was confirmed by bioanalytical methods.

Findings:

Between January 2017- November 2018, 74 men with urethritis and HIV and were confirmed ART naive. The median age was 32 years. Forty-one (55% of men) initiated ART within 1 week; 12 (16%) between 1–4 weeks; and 21 (28%) did not initiate ART by week 4. Within the 1 week group, median VL was suppressed within 4 weeks in both semen and blood. Among the 1–4 weeks group, VL was suppressed within 4 weeks in semen and 5 weeks in blood. Among the no ART before 4 weeks group, VL in semen declined within the first 4 weeks but remained unsuppressed through week 24, and there was no significant decline in blood HIV.

Conclusion:

Treatment of urethritis and prompt initiation of ART with counseling for safer sex for at least one month is a critical measure to reduce transmission of HIV.
Lentibacillus daqui sp. nov., isolated from high-temperature Daqu, a starter for production of Chinese Jiang-flavour Baijiu
Authors: Liang Yuan , Lu Zhen-Ming , Shi Wei , Wu Lin-Huan , Chai Li-Juan , Zhang Xiao-Juan , Zhang Su-Yi , Wang Song-Tao , Shen Cai-Hong , Xu Zheng-Hong
Published: August 2023

A Gram-stain-positive, rod-shaped, endospore-forming, aerobic bacterial strain, designated ZS110521T, was isolated from high-temperature Daqu, a starter for production of Chinese Jiang-flavour Baijiu and was characterised by polyphasic taxonomy. This novel isolate grew in the presence of 0–20 % (w/v) NaCl, at pH 6.0–9.0 and 20–50 °C; optimum growth was observed with 8–10 % (w/v) NaCl, at pH 7.0 and 37 °C. A comparative analysis of the 16S rRNA gene sequence (1460 bp) of ZS110521T revealed that it displayed the highest similarity to

Lentibacillus populi

WD4L-1T (95.5 %), followed by

Lentibacillus garicola

SL-MJ1T (95.4 %) and

Lentibacillus lacisalsi

BH260T (95.2 %). ANI and dDDH values between ZS110521T and other strains of species of the genus

Lentibacillus

were less than 78 and 28 %, respectively. The predominant cellular fatty acids (> 10 %) of ZS110521T were anteiso-C17 : 0 (37.8 %), anteiso-C15 : 0 (28.1 %) and iso-C16 : 0 (15.5 %). The respiratory quinone was identified as menaquinone-7 (MK-7) and the major polar lipids were diphosphatidylglycerol and phosphatidylglycerol. The polyphasic taxonomic data and the results of chemotaxonomic analysis confirmed that ZS110521T represents a novel species, for which the name Lentibacillus daqui sp. nov. is proposed. The type strain of this proposed species is ZS110521T (=CGMCC 1.19456T =JCM 35213T).
Paracoccus albicereus sp. nov., isolated from the shallow-sea hydrothermal system off Kueishantao Island
Authors: He Yajie , Lin Dan , Chen Beihan , Liu Xinzhu , Ye Jianing , Sun Jia , Tang Kai
Published: August 2023

Strain designated TK19116T was isolated from the shallow-sea hydrothermal systems off Kueishantao Island in Taiwan, China. The bacterium was Gram-stain-negative, aerobic, oxidase-positive and catalase-positive. Cells of the strain TK19116T were short-rod-shaped and non-motile. The results of phylogenetic analysis of 16S rRNA gene sequences indicated that strain TK19116T belonged to the genus

Paracoccus

, with the highest sequence similarity to

Paracoccus alkanivorans

4-2T (97.1 %). The average nucleotide identity values between the strain TK19116T with

Paracoccus alkanivorans

4-2T,

Paracoccus zhejiangensis

J6T,

Paracoccus siganidrum

M26T and

Paracoccus tegillarcae

BM15T were 75.3, 76.7, 76.7 and 75.8%, respectively. The digital DNA–DNA hybridization value between the strain TK19116T with

Paracoccus alkanivorans

4-2T,

Paracoccus zhejiangensis

J6T,

Paracoccus siganidrum

M26T and

Paracoccus tegillarcae

BM15T were 19.7, 20.3, 20.5 and 20.0%, respectively. The main respiratory quinone of strain TK19116T was ubiquinone 10. The polar lipids include aminolipid, phosphatidylcholine, diphosphatidylglycerol, glycolipid, phosphatidylglycerol and phospholipid. The principal fatty acid of strain TK19116T was summed feature 8 (C18 : 1
 ω6c and/or C18 : 1
 ω7c). The G+C content of the chromosomal DNA was 64.2 %. The combination of the results of the phylogenetic, phenotypic and chemotaxonomic analysis, strain TK19116T represents a novel species of the genus

Paracoccus

, for which the name Paracoccus albicereus sp. nov. is proposed. The type strain is TK19116T (= MCCC 1K08025T=JCM 35527T).
Normalization of Drug and Therapeutic Concepts with TheraPy
Authors: Cannon Matthew , Stevenson James , Kuzma Kori , Kiwala Susanna , Warner Jeremy L , Griffith Obi L , Griffith Malachi , Wagner Alex H
Published: August 2023

Working with therapeutic terminology in the field of medicine can be challenging due to both the number of ways terms can be addressed and the ambiguity associated with different naming strategies. A therapeutic concept can be identified across many facets from ontologies and vocabularies of varying focus, including natural product names, chemical structures, development codes, generic names, brand names, product formulations, or treatment regimens. This diversity of nomenclature makes therapeutic terminology difficult to manage and harmonize. As the number and complexity of available therapeutic ontologies continues to increase, the need for harmonized cross-resource mappings is becoming increasingly apparent. Harmonized concept mappings will enable the linking together of like-concepts despite source-dependent differences in data structure or semantic representation. To support these mappings, we introduce TheraPy, a Python package and web API that constructs stable, searchable merged concepts for drugs and therapeutic terminologies using publicly available resources and thesauri. By using a directed graph approach, TheraPy can capture commonly used aliases, trade names, annotations, and associations for any given therapeutic and combine them under a single merged concept record. Using this approach, we found that TheraPy tends to normalize therapeutic concepts to their underlying active ingredients (excluding non-drug therapeutics, e.g. radiation therapy, biologics), and unifies all available descriptors regardless of ontological origin. In this report, we highlight the creation of 16,069 unique merged therapeutic concepts from 9 distinct sources using TheraPy. Further, we analyze rates of normalization for therapeutic terms taken from publicly available vocabularies.
Graphical Learning and Causal Inference for Drug Repurposing
Authors: Xu Tao , Zhao Jinying , Xiong Momiao
Published: August 2023

Gene expression profiles that connect drug perturbations, disease gene expression signatures, and clinical data are important for discovering potential drug repurposing indications. However, the current approach to gene expression reversal has several limitations. First, most methods focus on validating the reversal expression of individual genes. Second, there is a lack of causal approaches for identifying drug repurposing candidates. Third, few methods for passing and summarizing information on a graph have been used for drug repurposing analysis, with classical network propagation and gene set enrichment analysis being the most common. Fourth, there is a lack of graph-valued association analysis, with current approaches using real-valued association analysis one gene at a time to reverse abnormal gene expressions to normal gene expressions.

To overcome these limitations, we propose a novel causal inference and graph neural network (GNN)-based framework for identifying drug repurposing candidates. We formulated a causal network as a continuous constrained optimization problem and developed a new algorithm for reconstructing large-scale causal networks of up to 1,000 nodes. We conducted large-scale simulations that demonstrated good false positive and false negative rates.

To aggregate and summarize information on both nodes and structure from the spatial domain of the causal network, we used directed acyclic graph neural networks (DAGNN). We also developed a new method for graph regression in which both dependent and independent variables are graphs. We used graph regression to measure the degree to which drugs reverse altered gene expressions of disease to normal levels and to select potential drug repurposing candidates.

To illustrate the application of our proposed methods for drug repurposing, we applied them to phase I and II L1000 connectivity map perturbational profiles from the Broad Institute LINCS, which consist of gene-expression profiles for thousands of perturbagens at a variety of time points, doses, and cell lines, as well as disease gene expression data under-expressed and over-expressed in response to SARS-CoV-2.