bluuebunny/crossref_metadata_2025 huggingface dataset:
GNAQ R183Q somatic mutation contributes to aberrant arteriovenous specification in Sturge–Weber syndrome through Notch signaling
Authors: Huang Lulu , Sun Hao , Liu Yixin , Xu Li , Hu Menghan , Yang Yijie , Wang Ning , Wu Yue , Guo Wenyi
Published: August 2023

Episcleral vasculature malformation is a significant feature of Sturge–Weber syndrome (SWS) secondary glaucoma, the density and diameter of which are correlated with increased intraocular pressure. We previously reported that the GNAQ R183Q somatic mutation was located in the SWS episclera. However, the mechanism by which GNAQ R183Q leads to episcleral vascular malformation remains poorly understood. In this study, we investigated the correlation between GNAQ R183Q and episcleral vascular malformation via surgical specimens, human umbilical vein endothelial cells (HUVECs), and the HUVEC cell line EA.hy926. Our findings demonstrated a positive correlation between episcleral vessel diameter and the frequency of the GNAQ R183Q variant. Furthermore, the upregulation of genes from the Notch signaling pathway and abnormal coexpression of the arterial marker EphrinB2 and venous marker EphB4 were demonstrated in the scleral vasculature of SWS. Analysis of HUVECs overexpressing GNAQ R183Q in vitro confirmed the upregulation of Notch signaling and arterial markers. In addition, knocking down of Notch1 diminished the upregulation of arterial markers induced by GNAQ R183Q. Our findings strongly suggest that GNAQ R183Q leads to malformed episcleral vasculatures through Notch‐induced aberrant arteriovenous specification. These insights into the molecular basis of episcleral vascular malformation will provide new pathways for the development of effective treatments for SWS secondary glaucoma.
Clinical Practice Guideline Recommendations in Pediatric Orthopaedic Injury: A Systematic Review
Authors: Moore Lynne , Drager Justin , Freire Gabrielle , Yanchar Natalie , Miller Anna N. , Ben Abdel Anis , Bérubé Mélanie , Tardif Pier-Alexandre , Gnanvi Janyce , Stelfox Henry T. , Beaudin Marianne , Stang Antonia , Beno Suzanne , Weiss Matthew , Labrosse Melanie , Zemek Roger , Gagnon Isabelle J. , Beaulieu Emilie , Berthelot Simon , Klassen Terry , Turgeon Alexis F. , Lauzier François , Gabbe Belinda , Carsen Sasha
Published: August 2023

Background:

Lack of adherence to recommendations on pediatric orthopaedic injury care may be driven by lack of knowledge of clinical practice guidelines (CPGs), heterogeneity in recommendations or concerns about their quality. We aimed to identify CPGs for pediatric orthopaedic injury care, appraise their quality, and synthesize the quality of evidence and the strength of associated recommendations.

Methods:

We searched Medline, Embase, Cochrane CENTRAL, Web of Science and websites of clinical organizations. CPGs including at least one recommendation targeting pediatric orthopaedic injury populations on any diagnostic or therapeutic intervention developed in the last 15 years were eligible. Pairs of reviewers independently extracted data and evaluated CPG quality using the Appraisal of Guidelines Research and Evaluation (AGREE) II tool. We synthesized recommendations from high-quality CPGs using a recommendations matrix based on the GRADE Evidence-to-Decision framework.

Results:

We included 13 eligible CPGs, of which 7 were rated high quality. Lack of stakeholder involvement and applicability (i.e., implementation strategies) were identified as weaknesses. We extracted 53 recommendations of which 19 were based on moderate or high-quality evidence.

Conclusions:

We provide a synthesis of recommendations from high-quality CPGs that can be used by clinicians to guide treatment decisions. Future CPGs should aim to use a partnership approach with all key stakeholders and provide strategies to facilitate implementation. This study also highlights the need for more rigorous research on pediatric orthopaedic trauma.

Level of Evidence:

Level II—therapeutic study.
The Evolving Therapeutics of Endothelial Disease
Authors: Huertas-Bello Marcela , Sabater Alfonso L. , Koo Ellen H.
Published: August 2023

Endothelial dysfunction is one of the leading indications for corneal transplantation. Globally, there is a shortage of donor corneas, which is partly because of the lack of eye banking resources in emerging countries. Given this global shortage, there is naturally heightened interest surrounding pharmacological agents, genetic therapy, and endothelial cell–based therapeutic modalities. Endothelial cells have limited mitotic capacity in vivo, and thus, studies have been conducted for their ex vivo expansion using mitogens. Similarly, pluripotent stem cells have been used to differentiate into human corneal endothelial cells with varying degrees of success. Different strategies have also been developed for injecting and delivering these cells into the human eye. This review aims to compile the information published on the latest advances in endothelial disease therapy.
A Retrospective Study Analyzing Opioid Prescription Practices in Hand Surgery from 2013 to 2019
Authors: Rangel India , Harrington Maya T. , Movtchan Nellie V. , Kandi Lyndsay A. , Janbieh Javier , Pollock Jordan R. , Kruger Erwin , Ko Jason H. , Teven Chad M.
Published: August 2023

Background:

The potential for opioid prescription medication addiction and abuse has been a growing concern in healthcare. It is not uncommon for hand surgery patients to be overprescribed opioid medication for postoperative pain management. The objective of this study was to characterize changes in opioid prescription practices of hand surgeons treating Medicare Part D patients from 2013 to 2019.

Methods:

A retrospective analysis of Medicare Part D prescriber data from 2013 to 2019 was conducted. This database provides information on drugs paid for under the Medicare Part D Prescription Drug Program. For each prescriber and medication, the dataset includes the total number of prescriptions dispensed (original prescriptions and number of refills), and total medication cost.

Results:

In 2013, the 10 most common medications prescribed totaled 114,409 prescriptions, with 89,701 (78.4%) opioid prescriptions. In 2019, the 10 most common medications prescribed totaled 164,955 prescriptions, with 109,665 (66.5%) opioid prescriptions. Although total opioid prescriptions dropped, there was a 22% increase in the total number of prescriptions written. The two most common medications prescribed, hydrocodone-acetaminophen and oxycodone-acetaminophen, totaled 75,796 in 2013, compared with 76,518 in 2019. The overall number of prescriptions for nonsteroidal anti-inflammatory drugs increased by 157%, and the percentage of total opioids prescribed declined by 7.9%.

Conclusions:

The increase in total opioid prescriptions from 2013 to 2019 by hand surgeons in the Medicare Part D Prescription Drug Program lags behind the recommended shift to nonopioid pain management. The reasons for the overall rise in prescriptions deserve further exploration.
Workplace Bias Affecting Applicants to Independent Plastic Surgery Residencies
Authors: Weidman Allan A. , Hernandez Alvarez Angelica , Valentine Lauren , Manstein Samuel M. , Comer Carly , Foppiani Jose , Sarac Benjamin A. , Janis Jeffrey E. , Lin Samuel J.
Published: August 2023

Background:

This study explores factors that encourage residents to apply to independent plastic surgery residencies to gain insight into whether they faced bias as a result of this decision.

Methods:

Resident applicants who applied to two academic independent plastic surgery residencies in 2021 and 2022 were emailed a survey consisting of 25 questions. Responses were collected anonymously and analyzed. Descriptive statistics were performed, and subgroup analyses were conducted with Fisher exact and Pearson χ
2 testing.

Results:

Thirty-nine complete responses were included for analysis (response rate 22.7%). Participants were asked what encouraged them to go into plastic surgery during residency. The most common reasons were scrubbing in on plastic surgery cases and interactions with plastic surgery faculty/residents, with each reason cited by 30 respondents (76.8%). Further, 20.5% of residents agreed or strongly agreed that they felt unsupported by their program director in their decision to apply into plastic surgery. Likewise, 64.1% of respondents agreed or strongly agreed to having experienced demeaning comments or jokes by faculty about their choice of plastic surgery. Consequently, 17.9% agreed or strongly agreed that they developed stress or anxiety due to how co-residents and/or faculty treated them regarding their decision to pursue plastic surgery.

Conclusions:

General surgery residents planning to apply to independent plastic surgery residency may experience workplace biases related to their career decision. An important opportunity exists to support independent applicants and to provide mentorship.
Drug co-administration in the tumor immune microenvironment of Hepatocellular carcinoma
Authors: Shao Yingying , Su Ranran , Wang Yu , Yin Shuangshuang , Pu Weiling , Koo Sangho , Yu Haiyang
Published: August 2023

The etiology and exact molecular mechanisms of primary hepatocellular carcinoma (HCC) remain unclear, and its incidence has continued to increase in recent years. Despite tremendous advances in systemic therapies such as molecularly targeted drugs, HCC has some of the worst prognoses owing to drug resistance, frequent recurrence, and metastasis. Hepatocellular carcinoma is a widespread disease and its progression is regulated by the immune system. Traditional Chinese medicine (TCM) has been gradually theorized and systematized to have a holistic regulatory role for use in the prevention and treatment of tumors. Although half of the patients with HCC receive systemic therapy, traditionally sorafenib or lenvatinib are used as first-line treatment modalities. TCM is also widely used in the treatment of HCC, and the same immune checkpoint inhibitors (ICIs) such as PD-L1 have also received much focus in the field of continuously changing cancer treatment. Owing to the high probability of resistance to specific drugs and unsatisfactory efficacy due to administration of chemotherapy in single doses, the combination of drugs is the newest therapeutic option for patients with tumors and has become increasingly prominent for treatment. In this article, the research progress on combination therapy in the immunology of HCC is reviewed and the unique advantages of synergistic anti-tumor therapy with combination drugs are highlighted to provide new solutions for the clinical treatment of tumors.

Graphical abstract:

http://links.lww.com/AHM/A65
Outcomes and Early Complications Using an Endothelium-in Pull-Through Descemet Membrane Endothelial Keratoplasty Technique With Preloaded Versus Surgeon-Loaded Donor Tissue in Fuchs Patients
Authors: Cho Kyongjin , Ali Muhammad , Heckenlaible Nicolas J. , Jabbour Samir , Jun Albert S. , Srikumaran Divya
Published: August 2023

Purpose:

This study aimed to compare outcomes and early complications using an endothelium-in pull-through Descemet membrane endothelial keratoplasty (DMEK) technique with preloaded versus surgeon-loaded donor tissue.

Methods:

Data from 163 eyes of 125 patients at the Wilmer Eye Institute diagnosed with Fuchs endothelial corneal dystrophy who underwent DMEK with or without cataract extraction using surgeon-loaded tissue (n = 83) or preloaded tissue (n = 80) were reviewed. Best-corrected visual acuity and early postoperative complications including small graft detachment (less than one third of the graft area), large graft detachment (more than one third), graft failure, and rebubbling were compared.

Results:

Baseline characteristics including age, sex, and visual acuity were not statistically different between the groups. Small graft detachment was observed in 18.1% of the surgeon-loaded and 22.5% of the preloaded group (P = 0.48), whereas large detachment occurred in 12.0% and 5.0%, respectively (P = 0.11). Among these, rebubbling was performed in 18 (21.7%) in the surgeon-loaded compared with 12 (15.0%) in the preloaded group (P = 0.27). The rebubbling rate of the combined procedure (cataract surgery and DMEK) was 21.8% and of DMEK alone was 7.7% (P = 0.048). Primary graft failure occurred in 2 surgeon-loaded cases (2.4%) and 1 preloaded case (1.3%) (P = 0.58). There was no difference in postoperative best-corrected visual acuity at 1 year (logarithm of the minimum angle of resolution 0.21 ± 0.25 for the surgeon-loaded vs. 0.16 ± 0.16 for the preloaded group, P = 0.23).

Conclusions:

DMEK surgery using preloaded endothelium-in tissue has comparable outcomes with surgeon-loaded endothelium-in tissue. However, there was a trend toward the lower rebubbling rate in DMEK alone compared with combined procedures.
Extended frontalis orbicularis oculi muscle flap shortening for treating refractory apraxia of eyelid opening associated with blepharospasm
Authors: Wang Yu-Chi , Lai Ya-Wei , Lee Chia-Chen , Huang Shu-Hung , Kuo Yur-Ren , Lai Chung-Sheng
Published: August 2023

Background:

Refractory apraxia of eyelid opening (AEO) is mostly unresponsive to botulinum toxin (BTx) and inevitably leads to functional blindness. To treat this challenging condition, an innovative surgical technique was proposed.

Methods:

The extended frontalis orbicularis oculi muscle (FOOM) flap shortening consisting of frontalis suspension, partial myectomy, and myotomy in situ of eyelid protractors was applied to treat refractory AEO associated with blepharospasm. The postoperative outcomes and patient satisfaction were evaluated.

Results:

Seven patients (mean ages 64.1 ± 3.9 years) of 14 eyelids in total had an average flap shortening distance of 24.4 ± 1.3 mm. During a mean follow-up of 31.6 ± 11.4 months, the average BTx dosage reduced from 58.6 ± 12. 1 units to 30.0 ± 8.2 units, with a mean injection interval decreasing from 2.3 ± 0.5 months to 4.1 ± 0.9 months (p < 0.05). Palpebral fissure height increased from 1.4 ± 0.5 mm to 7.9 ± 0.7 mm, and the disability scale decreased from 78.8% ± 7.2% to 12.6% ± 7.0% (p < 0.05). The postoperative BTx dosage and frequency were significantly reduced. All patients restored voluntary eyelid opening and reported high postoperative satisfaction (average Likert scale 4.6 ± 0.5).

Conclusion:

Extended FOOM flap shortening is an effective treatment to solve refractory AEO associated with blepharospasm.
Budd–Chiari Syndrome following COVID-19 infection: a case report
Authors: Sawaqed Seri S. , Urabi Heba M. , Al-thnaibat Mohammad H. , Bani-Hani Anas , Mohd Omar B. , Mohd Ahmed B. , Ghannam Reem A. , Hasan Hanan , Alabdallat Yasmeen J. , Khaity Abdulrhman
Published: August 2023

Introduction and importance:

Budd–Chiari Syndrome (BCS) is a rare disorder that affects the liver and is caused by blockage of the hepatic veins. Coronavirus disease 2019 (COVID-19) has been linked to an increased risk of developing BCS due to its ability to cause inflammation in the body, which can lead to clotting disorders.

Case presentation:

A 43-year-old female presented to the emergency department complaining of severe epigastric and right upper quadrant pain and progressive abdominal distention. Upon examination, investigation, and triphasic liver computed tomography with contrast, the patient was diagnosed with BCS.

Clinical discussion:

The patient was started on anticoagulant therapy with low-molecular-weight heparin and supportive treatment. She was hospitalized for 3 weeks and discharged on oral warfarin 5 mg/day after showing clinical improvement.

Conclusion:

Hepatosplenomegaly and abdominal distention after COVID-19 infection raise suspicion for BCS. Therefore, early detection of these signs is essential for immediate management.
Genetic Correlations between Migraine and Carpal Tunnel Syndrome
Authors: Wiberg Akira , Lucey Maria A. , Kleeman Sam , Kang Youngjoo , Ng Mike , Furniss Dominic
Published: August 2023

Background:

Surgical deactivation of extracranial nerve trigger sites is now well established as an effective treatment for migraine headache. Parallels have been drawn to median nerve decompression for carpal tunnel syndrome (CTS), and 2 previous studies have demonstrated an association between migraine and CTS. The authors sought to (1) substantiate these findings in a considerably larger UK cohort, and (2) investigate potential genetic associations between the 2 disorders.

Methods:

Nested case-control studies were conducted in the UK Biobank cohort of 401,656 individuals. Odds ratios were calculated for the association between migraine and CTS in the overall cohort and sex-stratified subsets. Genetic correlation between migraine and CTS was interrogated by linkage disequilibrium score regression, leveraging data from published genomewide association studies. Regions of genetic overlap were identified by multitrait analysis of genomewide association studies and cross-phenotype association.

Results:

Migraine and CTS show a significant epidemiologic association within UK Biobank (OR, 1.14, 95% CI, 1.04 to 1.25; P = 0.0058), which is specific to women (OR, 1.15; 95% CI, 1.04 to 1.28; P = 0.0057) and not men (OR, 1.07; 95% CI, 0.82 to 1.40; P = 0.61). Genetic analysis demonstrated a significant positive genetic correlation between the 2 disorders (r
g = 0.13; P = 0.0039), and implicated the TRIM32 locus on chromosome 9 as a region of genetic overlap.

Conclusions:

This study replicates past reports of an epidemiologic association between CTS and migraine, albeit in women only. This association is underpinned by a genetic correlation, with shared genetic susceptibility at the TRIM32 locus. The authors’ data add credibility to the notion that an element of entrapment neuropathy underlies migraine pathophysiology.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Risk, III.
Replacement of Shaped Textured Implants with Round Smooth Implants in Breast Reconstruction: Long-Term Outcomes
Authors: Ayyala Haripriya S. , Afifi Tarek , Castel Nikki , McCarthy Colleen , Cordeiro Peter G.
Published: August 2023

Background:

The number of patients undergoing exchange of textured implants for smooth devices has greatly increased because of concern over breast implant–associated anaplastic large-cell lymphoma (BIA-ALCL). The authors examined long-term patient- and surgeon-reported outcomes in terms of aesthetics, comfort, and complications.

Methods:

Patients who underwent reconstruction with shaped, textured implants replaced with round, smooth implants between 1994 and 2022 and who had a minimum follow-up of 1 year were included. Patient-reported outcomes were collected using the BREAST-Q Reconstruction module and a survey evaluating aesthetics and comfort. Surgeon-reported outcomes included evaluation of aesthetics and capsular contracture.

Results:

A total of 530 patients were reviewed, and 307 patients were included. Pairwise comparison of BREAST-Q data demonstrated that psychosocial well-being (72.68 to 76.45; P = 0.0075) and physical well-being (78.79 to 81.88; P = 0.0078) increased significantly. Overall breast satisfaction (61.94 to 67.27; P = 0.0082) and sexual well-being (53.89 to 57.98; P = 0.0002) were also significantly higher in parallel with a clinically meaningful increase in BREAST-Q score of 5.33 and 4.09 points, respectively. Most patients felt they appeared better (56.4%) or similar (27.3%) and were more comfortable (54.4%) or similar (39.4%) after the exchange procedure. The senior surgeon (P.G.C.) rated 40.1% of patients as having a better aesthetic grade after replacement and 50.3% as the same; 36.8% of patients were rated as having a decrease in Baker capsular contracture grade; 2.9% of patients experienced a perioperative complication; and there were no reconstructive failures.

Conclusion:

Exchange of textured to smooth implants is safe, does not sacrifice aesthetic outcome, and provides a more comfortable and satisfactory outcome for patients with minimal complications.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, IV.
Bilateral Lumbar Artery Perforator Flaps for Breast Reconstruction: A Perforator Classification System
Authors: Haddock Nicholas T. , Lakatta Alexis C. , Teotia Sumeet S.
Published: August 2023

Background:

Autologous breast reconstruction is continually evolving, with focus on the ideal donor site. This study presents 108 consecutive simultaneous lumbar artery perforator (LAP) flaps and a perforator classification system.

Methods:

A retrospective review of all LAP flaps was completed, and appropriate data were recorded. All simultaneous bilateral LAP flaps were included, and perforator patterns were assessed using CT angiography (CTA).

Results:

Fifty-four patients (108 flaps) were included in the final review. The mean patient age was 50.7 years, and the mean body mass index was 26.6. Mean ischemia times for all flaps and grafts were 130 ± 64.5 and 300.6 ± 97.3 minutes, respectively. The average pedicle length was 4.6 ± 1.5 cm, and the average composite graft length was 6.2 ± 1.7 cm. Donor-site complications consisted of seromas (10 patients [19%]), hematomas (6 patients [11%]), procedural wounds (4 patients [8%]), and infections (2 patients [4%]). The total flap loss rate was 2.8%. Perforators were classified into categories based on pedicle pattern, lumbar spine level, and clusters, all in relation to posterior iliac bone as seen per CTA. Vascular pedicle patterns were categorized as type 1 (43.9%), 2 (45.6%), 3 (8.8%), or 4 (1.8%). Perforators were dissected at lumbar spine level L3 in 51.8% of patients, L4 in 46.5%, and L5 in 1.8%.

Conclusions:

The authors present a CTA-directed anatomic perforator classification system to assist in preoperative planning, dissection, and choice of the composite graft best suited for particular perforator patterns or calibers. Simultaneous LAP flaps can be performed successfully with excellent outcomes in cases unsuitable for other flaps.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, IV.
Dual versus Single Innervation of Gracilis Free Functional Muscle Transfer in Facial Paralysis: Long-Term Resting and Dynamic Outcomes
Authors: Thachil Roshni , Wen Y. Edward , Madrazo Adolfo Zamaro , Sanchez Cristina V. , Reisch Joan S. , Rozen Shai M.
Published: August 2023

Background:

The purpose of this study was to compare long-term tone and excursion in single- versus dual-innervated free functional muscle transfer (FFMT) in patients with longstanding facial paralysis.

Methods:

Patients with longstanding facial palsy treated with an FFMT innervated either by a nerve-to-masseter graft (single-innervation group) or nerve-to-masseter and cross-facial-nerve grafts (dual-innervation group) were included. One-year minimum follow-up was required. Outcome measures, based on standardized photographs, included excursion, smile angle, teeth exposure, commissure height deviation, and upper lip height deviation in repose and in closed and open-teeth smile preoperatively and at 3 months, 1 year, and 3 years postoperatively. Emotrics software and ImageJ software were used to take measurements. Between-group and within-group longitudinal comparisons were analyzed.

Results:

At 3 years (single, n = 24; dual, n = 13), significance was found between groups in commissure position (single, 26.42 mm versus dual, 31.51 mm; P < 0.0001) and excursion with open-mouth smile (single, 31.32 mm versus dual, 26.59 mm; P < 0.001). Single-innervation FFMT within-group analysis lacked significant improvement in commissure height deviation and upper lip height deviation at 3 years in repose, whereas the dual-innervation group revealed significant improvements (3.67 mm [P < 0.001], 3.17 mm [P < 0.001], respectively). Teeth exposure revealed an increase in the dual-innervation group (single, 35.753 mm2 versus dual, 64.177 mm2), but significance was not observed.

Conclusion:

Dual-innervated FFMT revealed improvements in resting tone and teeth exposure with minimal decrease in smile excursion compared with single-innervated FFMT.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, III.
Educating Women About Pelvic Floor Disorders During Pregnancy From the First to the “Fourth Trimester”: A Randomized Clinical Trial
Authors: Rutledge Emily , Spiers Alaina , Vardeman Jennifer , Griffin Nickie , Nisar Tariq , Muir Tristi , Antosh Danielle D.
Published: August 2023

Importance

Pregnancy and childbirth are risk factors for developing pelvic floor disorders (PFDs), and this continues postpartum (“fourth trimester”). Knowledge of PFDs among women of childbearing age is lacking and presents an opportunity for education.

Objectives

The aim of this study was to compare the increase in knowledge of PFDs in patients who received written handouts versus interactive workshops as measured by the Prolapse and Incontinence Knowledge Questionnaire (PIKQ).

Study Design

This was a randomized clinical trial of pregnant patients 18 years or older. Patients either received written handouts only or received handouts and attended an interactive workshop. Handouts were created in collaboration with communication specialists focusing on risk factors and prevention strategies. The primary outcome was the change in PIKQ score. Secondary outcomes were Pelvic Floor Distress Inventory score and postpartum phone interviews of workshop group participants. Questionnaires were assessed at recruitment and 6 weeks postpartum. The nonparametric Wilcoxon test compared continuous variables, and the Fisher exact test compared categorical variables.

Results

One hundred twenty patients were randomized. Demographics were similar between groups. Median PIKQ score change showed no difference between groups (P = 0.37). Pelvic Floor Distress Inventory-20 scores were similar between groups at baseline (P = 0.78) and postpartum (P = 0.82). Quantile regression showed posteducation PIKQ scores were significantly higher in the workshop (21.00 vs 17.00; P = 0.011) and written (21.00 vs 17.00; P < 0.001) groups. Phone interviews showed consistent themes: (1) greater awareness of PFDs, (2) more likely to discuss PFDs, and (3) relief that PFDs are treatable. Fifty-nine percent of patients preferred learning through workshops compared with the handouts.

Conclusions

Both groups showed improvement in knowledge of PFDs. Well-written, illustrated handouts were effective in increasing patient knowledge of PFDs.
Functional connectivity of the default mode network predicts subsequent polysomnographically measured sleep in people with symptoms of insomnia
Authors: Killgore William D.S. , Jankowski Samantha , Henderson-Arredondo Kymberly , Lucas Daniel A. , Patel Salma I. , Hildebrand Lindsey L. , Huskey Alisa , Dailey Natalie S.
Published: August 2023

Insomnia is often accompanied by excessive pre-sleep rumination. Such ruminative thinking is also associated with increased connectivity of the default mode network (DMN). It is likely that DMN connectivity and associated rumination contribute to the pathogenesis of insomnia. We hypothesized that resting state functional connectivity (rsFC) between the DMN and other brain regions prior to bedtime would predict objectively measured sleep among individuals with insomnia. Twenty participants (12 female; Mage = 26.9, SD = 6.6 years) with symptoms of insomnia underwent an rsFC scan in the early evening followed by a night of polysomographically (PSG) measured sleep. Connectivity of the DMN with other brain regions was regressed against several PSG sleep metrics, including time in wake, N1, N2, N3, REM, total sleep time (TST), and sleep efficiency (SE) at a cluster corrected false discovery rate (FDR) correction P< 0.05. The connectivity between DMN and cortical regions was negatively correlated with PSG indices of poorer sleep including time in wake (right angular gyrus) and N1 (precuneus) but positively correlated with time in REM (orbitofrontal cortex), TST (insula, orbitofrontal cortex, superior frontal gyrus, paracingulate gyrus), SE (orbitofrontal cortex). Connectivity between DMN and the pons was negatively correlated with SE. Among individuals with symptoms of insomnia, better sleep was predicted by rsFC between the DMN and cortical regions involved in executive functioning, consciousness, and complex cognition. Findings raise the possibility that future interventions aimed at suppressing pre-sleep DMN activation may weaken synergy between pre-sleep ruminative worry and complex cognitions, potentially ameliorating problems falling asleep.
Palaeoecological deductions from osteohistology
Authors: Chinsamy Anusuya
Published: August 2023

Palaeoecological deductions are vital for understanding the evolution and diversification of species within prehistoric environments. This review highlights the multitude of ways in which the microanatomy and microscopic structure of bones enables palaeoecological deductions. The occurrence of growth marks in bones is discussed, and their usefulness in deducing the ontogenetic status and age of individuals is considered, as well as how such marks in bones permit the assessment of the growth dynamics of individuals and species. Here osteohistology is shown to provide insight into the structure of past populations, as well as ecological relationships between individuals. In addition, the response of bones to trauma, disease and moulting is considered. Finally, I explore how osteohistology can give insight into ecomorphological adaptations, such as filter feeding, probe feeding and saltatorial locomotion. Methodological advances in three-dimensional microtomography and synchrotron scanning bodes well for future studies in osteohistology and despite some compromises in terms of tissue identity, circumvents the crucial issue of destructive analyses.
Triple-spherical Bessel function integrals with exponential and Gaussian damping: towards an analytic N-point correlation function covariance model
Authors: Chellino Jessica , Slepian Zachary
Published: August 2023

Spherical Bessel functions (sBFs) appear commonly in many areas of physics wherein there is both translation and rotation invariance, and often integrals over products of several arise. Thus, analytic evaluation of such integrals with different weighting functions (which appear as toy models of a given physical observable, such as the galaxy power spectrum) is useful. Here, we present a generalization of a recursion-based method for evaluating such integrals. It gives relatively simple closed-form results in terms of Legendre functions (for the exponentially damped case) and Gamma, incomplete Gamma, and hypergeometric functions (for the Gaussian-damped case). We also present a new, non-recursive method to evaluate integrals of products of sBFs with Gaussian damping in terms of incomplete Gamma functions and hypergeometric functions.
Overlapping transmission of group A and C/GStreptococcusfacilitates inter-species mobile genetic element exchange
Authors: Xie Ouli , Zachreson Cameron , Tonkin-Hill Gerry , Price David J , Lacey Jake A , Morris Jacqueline M , McDonald Malcolm I , Bowen Asha C , Giffard Philip M , Currie Bart J , Carapetis Jonathan R , Holt Deborah C , Bentley Stephen D , Davies Mark R , Tong Steven YC
Published: August 2023

Streptococcus dysgalactiaesubspeciesequisimilis(SDSE) andStreptococcus pyogenesshare skin and throat niches with extensive genomic homology and horizontal gene transfer (HGT) possibly underlying shared disease phenotypes. It is unknown if cross-species transmission interaction occurs. We conducted a genomic analysis of a longitudinal household survey in remote Australian First Nations communities for patterns of cross-species transmission interaction and HGT. From 4,547 person-consultations, 294 SDSE and 315S. pyogenesisolates were sequenced. SDSE andS. pyogenestransmission intersected extensively among households and the observed co-occurrence and transmission links were consistent with independent transmission without inter-species interference. At least one of three near-identical cross-species mobile genetic elements (MGEs) carrying antimicrobial resistance or streptodornase virulence genes was found in 55 (19%) SDSE and 23 (7%)S. pyogenesisolates. These findings demonstrate extensive co-circulation of both pathogens and HGT and support a need to integrate SDSE andS. pyogenessurveillance and control efforts.
A physiologically-based digital twin for alcohol consumption – predicting real-life drinking responses and long-term plasma PEth
Authors: Podéus Henrik , Simonsson Christian , Nasr Patrik , Ekstedt Mattias , Kechagias Stergios , Lundberg Peter , Lövfors William , Cedersund Gunnar
Published: August 2023

Alcohol consumption is associated with a wide variety of preventable health complications and is a major risk factor for all-cause mortality in the age group 15-47 years. To reduce dangerous drinking behavior, eHealth applications have shown promise. A particularly interesting potential lies in the combination of eHealth apps with mathematical models. However, existing mathematical models do not consider real-life situations, such as combined intake of meals and beverages, and do not connect drinking to clinical markers, such asphosphatidylethanol(PEth). Herein, we present such a model which can simulate real-life situations and connect drinking to long-term markers. The new model can accurately describe both estimation data according to a χ2-test (187.0 < Tχ2= 226.4) and independent validation data (70.8 < Tχ2=93.5). The model can also be personalized using anthropometric data from a specific individual and can thus be used as a physiologically-based digital twin. This twin is also able to connect short-term consumption of alcohol to the long-term dynamics of PEth levels in the blood, a clinical biomarker of alcohol consumption. Here we illustrate how connecting short-term consumption to long-term markers allows for a new way to determine patient alcohol consumption from measured PEth levels. An additional use case of the twin could include the combined evaluation of patient-reported AUDIT forms and measured PEth levels. Finally, we integrated the new model into an eHealth application, which could help guide individual users or clinicians to help reduce dangerous drinking.
A risk stratification model for high-flow nasal cannula use in patients with coronavirus disease 2019 in Japan: a single-center retrospective observational cohort study
Authors: Kurihara Ibuki , Sugawara Hitoshi
Published: August 2023

Background

The coronavirus disease 2019 (COVID-19) pandemic has put a strain on the healthcare system, and sudden changes in disease status during home treatment have become a serious issue. Therefore, prediction of disease severity and allocation of sufficient medical resources, including high-flow nasal cannula (HFNC), to patients in need are important. We aimed to determine risk factors for the need of HFNC use in COVID-19.

Methods

This was a single-center retrospective observational cohort study including all eligible hospitalized adult patients aged ≥18 years diagnosed with COVID-19 between April 14, 2020 and August 5, 2021 who were treated in the study hospital. The primary outcome was critical respiratory illness meeting one of the following criteria: oxygenation flow rate ≥ 10 L/min, high-flow oxygenation, noninvasive ventilation, invasive ventilation, and death. Nineteen potential predictive variables, including patient characteristics at hospital admission, were screened using least absolute shrinkage and selection operator and logistic regression to construct a predictive risk score. Accuracy of the risk score was determined using area under the receiver operating characteristic curve.

Results

The study cohort included 148 patients. The rate of critical respiratory illness was 22.9% (all patients needed high-flow device support). Among the 19 potential variables, percutaneous oxygen saturation (SpO2) <92% (odds ratio [OR] 7.50, 95% confidence interval [CI] 2.806–20.82) and IL-6 (OR 1.021, 95% CI 1.010–1.033) were included in developing the risk score, which was termed interleukin (IL)-6-based COVID-19 severity (IBC-S) score.

Conclusions

The IBC-S score, an easy-to-use risk score based on parameters available at the time of hospital admission, predicted critical respiratory failure in patients with COVID-19. In primary care settings, the IBC-S score based on interleukin-6 and SpO2 might aid in determining patients who should be transported to a tertiary medical institution or an isolation facility.
Plasticity, geographic variation and trait coordination in blue oak drought physiology
Authors: Anderegg Leander D.L. , Skelton Robert P. , Diaz Jessica , Papper Prahlad , Ackerly David D. , Dawson Todd E.
Published: August 2023

Our ability to predict drought stress across the landscape remains limited. This uncertainty stems in part from an incomplete understanding of within-species variation in hydraulic physiology, particularly coordinated variation across multiple traits. This variation reflects genetic differentiation among populations (ecotypic variation) and phenotypic plasticity. We examined among-population differentiation in morphological and hydraulic traits in California blue oak (Quercus douglasii) using a 30 year-old common garden. We compared trait differentiation and trait-trait coordination in the garden to wild phenotypes from the original source populations. We found remarkably limited among-population differentiation in all traits in the common garden but considerable site-to-site variation in the field that could rarely be explained with site climate variables. Trait-trait relationships were also stronger in the field than in the garden, particularly links between leaf morphology, leaf hydraulic efficiency and stem hydraulic efficiency. Only four trait-trait relationship were present in both the wild and garden, but 12 of 45 relationships showed significant wild phenotypic correlations, with strong coordination among leaf and stem hydraulic efficiency apparently mediated by leaf size. Ultimately, we found limited evidence for ecotypic variation but considerable geographic in phenotypic integration in the wild, suggesting considerable acclimation potential in the face of climate change.
The risk of future mpox outbreaks among men who have sex with men: a modelling study based on cross-sectional seroprevalence data
Authors: Shamier Marc C. , Zaeck Luca M. , Götz Hannelore M. , Vieyra Bruno , Verstrepen Babs E. , Wijnans Koen , Welkers Matthijs R.A. , Hoornenborg Elske , van Royen Martin E. , Jonas Kai J. , Koopmans Marion P.G. , de Vries Rory D. , van de Vijver David A.M.C. , GeurtsvanKessel Corine H.
Published: August 2023

Structured abstract

Background

In the wake of the 2022-2023 mpox outbreak, crucial knowledge gaps exist regarding orthopoxvirus-specific immunity in risk groups and its impact on future outbreaks.

Aim

This study combined cross-sectional seroprevalence studies in two cities in the Netherlands with mathematical modelling to evaluate the risk of future mpox outbreaks among men who have sex with men (MSM).

Methods

Serum samples were obtained from 1,065 MSM visiting the Centres for Sexual Health (CSH) in Rotterdam or Amsterdam after the introduction of vaccination and the peak of the Dutch mpox outbreak. For MSM visiting the CSH in Rotterdam, sera were linked to epidemiological and vaccination data. An in-house developed ELISA was used to detect vaccinia virus (VACV)- specific IgG. These observations were combined with literature data on infection dynamics and vaccine effectiveness to inform a stochastic transmission model to estimate the risk on future mpox outbreaks.

Results

The seroprevalence of VACV-specific antibodies was 45.4% and 47.1% in Rotterdam and Amsterdam, respectively. Transmission modelling showed that the impact of risk group vaccination on the original outbreak was likely small; however, the number of mpox cases in a future outbreak would be markedly reduced because of vaccination. Simultaneously, the current level of immunity alone may not prevent future outbreaks. Maintaining a short time-to-diagnosis will be a key component of any strategy to prevent new outbreaks.

Discussion

Our findings indicate a reduced likelihood of future mpox outbreaks among MSM in the Netherlands under the current conditions, but emphasise the importance of maintaining population immunity, diagnostic capacities, and disease awareness.
Findings from a Pilot of a Near Real Time Disease Surveillance Tool on the NATO Mission in Kosovo
Authors: Lindfield Robert , Biendl Claudia , Toth Mate , Ruhl Silke
Published: August 2023

NATO has a requirement for a near real time surveillance (NRTS) tool to rapidly identify disease outbreaks but no deployable tool is available. The NATO Centre of Excellence for Military Medicine (MILMED COE) developed a NRTS tool and piloted it on the NATO Mission in Kosovo (KFOR).

Ten medical treatment facilities (MTFs) in KFOR piloted the tool which is an app on a smart device. All first presentations were eligible for inclusion into the app. Primary presenting symptoms were mapped to one or more of 40 symptoms. No patient identifiable information was collected. Analysis was available to each MTF and the Medical HQ staff (JMED) which provided a summary of the data collected. Combinations of symptoms resulted in an alert email to the JMED and MTF.

An evaluation was conducted at two time points consisting of data analysis and semi-structured interviews with key informants from each participating MTF and JMED team.

1351 patients were entered during the pilot. 851 reports had symptoms recorded. The leading symptoms were pain-in-throat, cough and temperature. Two investigations were launched based on reporting in the app; a cluster of skin lesions and two cases of diarrhoea. No significant outbreaks were reported during the pilot or detected by the app.

Interviews revealed that the app was easy to use and the symptom list was comprehensive. The analysis tool was not regularly viewed by MTFs however the JMED team used it frequently. Alerts were considered extremely valuable by both the MTFs and JMED team.

The KFOR pilot provided an excellent opportunity to pilot the tool in a NATO Mission and established that the way it collected data and alerted issues worked well. Further validation and analysis of the tool is required before it can be rolled out further.
Relationship of plasma biomarkers to digital cognitive tests in alzheimer’s disease
Authors: Toniolo Sofia , Zhao Sijia , Scholcz Anna , Amein Benazir , Ganse-Dumrath Akke , Heslegrave Amanda J , Thompson Sian , Manohar Sanjay , Zetterberg Henrik , Husain Masud
Published: August 2023

Introduction

A major limitation in Alzheimer’s disease (AD) research is the lack of the ability to measure cognitive performance at scale - robustly, remotely, and frequently. Currently, there are no established online digital platforms validated against plasma biomarkers of AD.

Methods

We used a novel web-based platform that assessed different cognitive functions in AD patients (N=46) and elderly controls (N=53) who were also evaluated for plasma biomarkers (amyloid β42/40 ratio, pTau181, GFAP, NfL). Their cognitive performance was compared to a second, larger group of elderly controls (N=352).

Results

Patients with AD were significantly impaired across all digital cognitive tests, with performance correlating with plasma biomarker levels, particularly pTau181. The combination of pTau181 and the single best-performing digital test achieved high accuracy in group classification.

Discussion

These findings show how online testing can now be deployed in patients with AD to measure cognitive function effectively and related to blood biomarkers of the disease.
Insights into the Mechanisms and Structure of Breakage-Fusion-Bridge Cycles in Cervical Cancer using Long-Read Sequencing
Authors: Rodriguez Isabel , Rossi Nicole M. , Keskus Ayse , Xie Yi , Ahmad Tanveer , Bryant Asher , Lou Hong , Paredes Jesica Godinez , Milano Rose , Rao Nina , Tulsyan Sonam , Boland Joseph F. , Luo Wen , Liu Jia , O’Hanlon Tim , Bess Jazmyn , Mukhina Vera , Gaykalova Daria , Yuki Yuko , Malik Laksh , Billingsley Kimberley , Blauwendraat Cornelis , Carrington Mary , Yeager Meredith , Mirabello Lisa , Kolmogorov Mikhail , Dean Michael
Published: August 2023

Cervical cancer is caused by human papillomavirus (HPV) infection, has few approved targeted therapeutics, and is the most common cause of cancer death in low-resource countries. We characterized 19 cervical and four head and neck cell lines using long-read DNA and RNA sequencing and identified the HPV types, HPV integration sites, chromosomal alterations, and cancer driver mutations. Structural variation analysis revealed telomeric deletions associated with DNA inversions resulting from breakage-fusion-bridge (BFB) cycles. BFB is a common mechanism of chromosomal alterations in cancer, and this is one of the first analyses of these events using long-read sequencing. Analysis of the inversion sites revealed staggered ends consistent with exonuclease digestion of the DNA after breakage. Some BFB events are complex, involving inter- or intra-chromosomal insertions or rearrangements. None of the BFB breakpoints had telomere sequences added to resolve the dicentric chromosomes and only one BFB breakpoint showed chromothripsis. Five cell lines have a Chr11q BFB event, withYAP1/BIRC2/BIRC3gene amplification. Indeed,YAP1amplification is associated with a 10-year earlier age of diagnosis of cervical cancer and is three times more common in African American women. This suggests that cervical cancer patients withYAP1/BIRC2/BIRC3-amplification, especially those of African American ancestry, might benefit from targeted therapy. In summary, we uncovered new insights into the mechanisms and consequences of BFB cycles in cervical cancer using long-read sequencing.
Patients Accessing their Online Records in England: A Survey of General Practitioners’ Experiences and Opinions
Authors: Blease Charlotte , Kharko Anna , Dong Zhiyong , Jones Ray , Davidge Gail , Hägglund Maria , Turner Andrew , DesRoches Catherine M. , McMillan Brian
Published: August 2023

Objective

To describe the experiences and opinions of general practitioners (GPs) in England regarding patients having access to their full online GP health record.

Design

Convenience sample, online survey.

Participants

400 registered GPs in England.

Main outcome measures

Investigators measured GPs’ experiences and opinions about online record access (ORA) including on patient care, and on their practice.

Results

A total of 400 GPs from all regions of England responded. A minority (130, 33%) believed ORA was a good idea. Most GPs believed a majority of patients would worry more (364, 91%) or find their GP records more confusing than helpful (338, 85%). In contrast, most GPs believed a majority of patients would find significant errors in their records (240, 60%), would better remember their care plan (280, 70%), and feel more in control of their care (243, 60%). The majority believed they will/already spend more time addressing patients’ questions outside of consultations (357, 89%), that consultations will/already take significantly longer (322, 81%), and reported they will be/already are less candid in their documentation (289, 72%) after ORA. Nearly two thirds of GPs believed ORA would increase their litigation (246, 62%).

Conclusions

Similar to clinicians in other countries, GPs in our sample were sceptical of ORA believing patients would worry more and find their records more confusing than helpful. Most GPs also believed the practice would exacerbate work burdens. However, the majority of GPs in this survey also agreed there were multiple benefits to patients having online access to their primary care health record.