bluuebunny/crossref_metadata_2025 huggingface dataset:
Racial disparity in uterine leiomyoma: new insights of genetic and environmental burden in myometrial cells
Authors: Khan Nazeer H , McNally Ross , Kim J Julie , Wei Jian-Jun
Published: January 2024

Uterine leiomyoma (LM), also known as uterine fibroids, are common gynecological tumors and can reach a prevalence of 70% among women by the age of 50 years. Notably, the LM burden is much higher in Black women with earlier onset, a greater tumor number, size, and severity compared to White women. Published knowledge shows that there are genetic, environmental, and lifestyle-based risk factors associated with racial disparity for LM. Significant strides have been made on genomic, epigenomic, and transcriptomic data levels in Black and White women to elucidate the underlying pathomolecular reasons of racial disparity in LM development. However, racial disparity of LM remains a major area of concern in gynecological research. This review highlights risk factors of LM and their role in different races. Furthermore, we discuss the genetics and uterine myometrial microenvironment in LM development. Comparative findings revealed that a major racial difference in the disease is linked to myometrial oxidative burden and altered ROS pathways which is relevant to the oxidized guanine in genomic DNA and MED12 mutations that drive the LM genesis. Considering the burden and morbidity of LM, we anticipate that this review on genetic risk and myometrial microenvironment will strengthen understanding and propel the growth of research to address the racial disparity of LM burden.
Comprehensive analysis of ovarian granulosa cell proteomics and phosphoproteomics in PCOS patients without insulin resistance
Authors: Yang Xiao , Liu Peng , He Hongcheng , Qi Dan , Yan Lei
Published: January 2024

PCOS is a complex and heterogeneous metabolic disorder that affects 6–20% of women of reproductive age. However, research on phosphorylation modification proteomics in PCOS remains lacking. PCOS can be divided into two groups based on the presence or absence of insulin resistance: PCOS with insulin resistance (PCOS-IR) and PCOS non-insulin resistant (PCOS-NIR). This study focused on the group without insulin resistance. Twenty-one PCOS-NIR and 39 control-NIR (Ctrl-NIR) patients were included in this study. All participants underwent ICSI or IVF-embryo transfer (IVF-ET) treatment in a reproductive center from July 2020 to November 2020. During oocyte retrieval, fresh follicular fluid was aspirated, collected, and sent to the laboratory for analysis of the granulosa cells. A 4D-label-free proteome quantification method was performed in this study; this was used to analyze protein enzymatic peptide fragments by liquid chromatography–mass spectrometry (LC–MS). Bioinformatic analysis was performed on differentially expressed proteins (DEPs) and differentially phosphorylated proteins (DPPs). A total of 713 DEPs were identified between the two groups, including 293 upregulated and 420 downregulated DEPs in the PCOS-NIR group. There were 522 and 159 proteins with increased and decreased phosphorylation, respectively, in the PCOS-NIR group. After analyzing the different phosphorylation modification sites, 933 sites with upregulated and 211 sites with downregulated phosphorylation were found in the PCOS-NIR group. In this study, we describe the quantitative protein expression profiles and phosphorylation-modified protein expression profiles of ovarian granulosa cells from patients with PCOS-NIR, providing a new research perspective for these patients. Further studies are required to elucidate the role of protein phosphorylation in PCOS.
Antioxidant and anti-inflammatory injectable hydrogel microspheres for in situ treatment of tendinopathy
Authors: Han Qibin , Bai Lang , Qian Yinhua , Zhang Xiaoyu , Wang Juan , Zhou Jing , Cui Wenguo , Hao Yuefeng , Yang Xing
Published: January 2024

Tendinopathy is a common disorder that causes local dysfunction and reduces quality of life. Recent research has indicated that alterations in the inflammatory microenvironment play a vital role in the pathogenesis of tendinopathy. Herein, injectable methacrylate gelatin (GelMA) microspheres (GM) were fabricated and loaded with heparin-dopamine conjugate (HDC) and hepatocyte growth factor (HGF). GM@HDC@HGF were designed to balance the inflammatory microenvironment by inhibiting oxidative stress and inflammation, thereby regulating extracellular matrix (ECM) metabolism and halting tendon degeneration. Combining growth factors with heparin was expected to improve the encapsulation rate and maintain the long-term efficacy of HGF. In addition, the catechol groups on dopamine have adhesion and antioxidant properties, allowing potential attachment at the injured site, and better function synergized with HGF. GM@HDC@HGF injected in situ in rat Achilles tendinopathy (AT) models significantly down-regulated oxidative stress and inflammation, and ameliorated ECM degradation. In conclusion, the multifunctional platform developed presents a promising alternative for the treatment of tendinopathy.
COVID-19 vaccination during pregnancy and adverse perinatal outcomes: a systematic review and meta-analysis
Authors: Wang Jia , Deng Yuzhi , Wang Weijing
Published: January 2024

We aimed to estimate the associations between coronavirus disease 2019 (COVID-19) vaccination during pregnancy and the risks of adverse perinatal outcomes. We performed a literature search in PubMed, Web of Science and Embase to identify eligible studies published up to 24 September 2023, yielding 39 included studies. Pooled relative risks (RRs) with 95% confidence intervals (CIs) were calculated with a random effects model. The pooled results showed that COVID-19 vaccination during pregnancy (any type or dose of COVID-19 vaccination during any trimester) was not associated with an increased risk of adverse perinatal outcomes. In particular, COVID-19 vaccination in the third trimester was associated with a decreased risk of preterm birth (<37 weeks) (RR 0.85 [95% CI 0.74 to 0.98]), 5-min Apgar <7 (RR 0.87 [95% CI 0.78 to 0.97]) and neonatal intensive care unit (NICU) admission (RR 0.90 [95% CI 0.86 to 0.95]). The inverse associations were also found in analysis of one-dose vaccination during pregnancy and the risk of miscarriage (RR 0.83 [95% CI 0.72 to 0.96]) and preterm birth (<37 weeks) (RR 0.90 [95% CI 0.80 to 1.00]) and two-dose vaccination during pregnancy and the risk of NICU admission (RR 0.86 [95% CI 0.76 to 0.96]). COVID-19 vaccination during pregnancy does not increase the risk of negative outcomes for the mother or baby.
The serum small non‐coding RNA (SncRNA) landscape as a molecular biomarker of age associated muscle dysregulation and insulin resistance in older adults
Authors: Burton Mark A. , Antoun Elie , Garratt Emma S. , Westbury Leo , Dennison Elaine M. , Harvey Nicholas C. , Cooper Cyrus , Patel Harnish P. , Godfrey Keith M. , Lillycrop Karen A.
Published: January 2024

Small noncoding RNAs (sncRNAs) are implicated in age‐associated pathologies, including sarcopenia and insulin resistance (IR). As potential circulating biomarkers, most studies have focussed on microRNAs (miRNAs), one class of sncRNA. This study characterized the wider circulating sncRNA transcriptome of older individuals and associations with sarcopenia and IR. sncRNA expression including miRNAs, transfer RNAs (tRNAs), tRNA‐associated fragments (tRFs), and piwi‐interacting RNAs (piRNAs) was measured in serum from 21 healthy and 21 sarcopenic Hertfordshire Sarcopenia Study extension women matched for age (mean 78.9 years) and HOMA2‐IR. Associations with age, sarcopenia and HOMA2‐IR were examined and predicted gene targets and biological pathways characterized. Of the total sncRNA among healthy controls, piRNAs were most abundant (85.3%), followed by tRNAs (4.1%), miRNAs (2.7%), and tRFs (0.5%). Age was associated (FDR < 0.05) with 2 miRNAs, 58 tRNAs, and 14 tRFs, with chromatin organization, WNT signaling, and response to stress enriched among gene targets. Sarcopenia was nominally associated (p < .05) with 12 tRNAs, 3 tRFs, and 6 piRNAs, with target genes linked to cell proliferation and differentiation such as Notch Receptor 1 (NOTCH1), DISC1 scaffold protein (DISC1), and GLI family zinc finger‐2 (GLI2). HOMA2‐IR was nominally associated (p<0.05) with 6 miRNAs, 9 tRNAs, 1 tRF, and 19 piRNAs, linked with lysine degradation, circadian rhythm, and fatty acid biosynthesis pathways. These findings identify changes in circulating sncRNA expression in human serum associated with chronological age, sarcopenia, and IR. These may have clinical utility as circulating biomarkers of ageing and age‐associated pathologies and provide novel targets for therapeutic intervention.
High Intraoperative Serum Lactate Level is Associated with Acute Kidney Injury after Brain Tumor Resection
Authors: Choi Seungeun , You Jiwon , Kim Yoon Jung , Lee Hyung-Chul , Park Hee-Pyoung , Park Chul-Kee , Oh Hyongmin
Published: January 2024

Background:

Postoperative acute kidney injury (AKI) is associated with poor clinical outcomes. Identification of risk factors for postoperative AKI is clinically important. Serum lactate can increase in situations of inadequate oxygen delivery and is widely used to assess a patient’s clinical course. We investigated the association between intraoperative serum lactate levels and AKI after brain tumor resection.

Methods:

Demographics, medical and surgical history, tumor characteristics, surgery, anesthesia, preoperative and intraoperative blood test results, and postoperative clinical outcomes were retrospectively collected from 4131 patients who had undergone brain tumor resection. Patients were divided into high (n=1078) and low (n=3053) lactate groups based on an intraoperative maximum serum lactate level of 3.35 mmol/L. After propensity score matching, 1005 patients were included per group. AKI was diagnosed using the Kidney Disease Improving Global Outcomes criteria, based on serum creatinine levels within 7 days after surgery.

Results:

Postoperative AKI was observed in 53 (1.3%) patients and was more frequent in those with high lactate both before (3.2% [n=35] vs. 0.6% [n=18]; P < 0.001) and after (3.3% [n=33] vs. 0.6% [n=6]; P < 0.001) propensity score matching. Intraoperative predictors of postoperative AKI were maximum serum lactate levels > 3.35 mmol/L (odds ratio [95% confidence interval], 3.57 [1.45–8.74], P = 0.005), minimum blood pH (odds ratio per 1 unit, 0.01 [0.00–0.24], P = 0.004), minimum hematocrit (odds ratio per 1%, 0.91 [0.84–1.00], P = 0.037), and mean serum glucose levels > 200 mg/dL (odds ratio, 6.22 [1.75–22.16], P = 0.005).

Conclusion:

High intraoperative serum lactate levels were associated with AKI after brain tumor resection.
Contribution of Tinnitus and Hearing Loss to Depression: NHANES Population Study
Authors: Chakrabarty Sayan , Mudar Raksha , Chen Yuguo , Husain Fatima T.
Published: January 2024

Objectives:

Hearing loss affects the emotional well-being of adults and is sometimes associated with clinical depression. Chronic tinnitus is highly comorbid with hearing loss and separately linked with depression. In this article, the authors investigated the combined effects of hearing loss and tinnitus on depression in the presence of other moderating influences such as demographic, lifestyle, and health factors.

Design:

The authors used the National Health and Nutrition Examination Survey data (2011–2012 and 2015–2016) to determine the effects of hearing loss and tinnitus on depression in a population of US adults (20 to 69 years). The dataset included the Patient Health Questionnaire-9 for depression screening, hearing testing using pure-tone audiometry, and information related to multiple demographic, lifestyle, and health factors (n = 5845).

Results:

The statistical analysis showed moderate to high associations between depression and hearing loss, tinnitus, and demographic, lifestyle, and health factors, separately. Results of logistic regression analysis revealed that depression was significantly influenced by hearing loss (adjusted odds ratios [OR] = 3.0), the functional impact of tinnitus (adjusted OR = 2.4), and their interaction, both in the absence or presence of the moderating influences. The effect of bothersome tinnitus on depression was amplified in the presence of hearing loss (adjusted OR = 2.4 in the absence of hearing loss to adjusted OR = 14.9 in the presence of hearing loss). Conversely, the effect of hearing loss on depression decreased when bothersome tinnitus was present (adjusted OR = 3.0 when no tinnitus problem was present to adjusted OR = 0.7 in the presence of bothersome tinnitus).

Conclusions:

Together, hearing loss and bothersome tinnitus had a significant effect on self-reported depression symptoms, but their relative effect when comorbid differed. Tinnitus remained more salient than hearing loss and the latter’s contribution to depression was reduced in the presence of tinnitus, but the presence of hearing loss significantly increased the effects of tinnitus on depression, even when the effects of the relevant demographic, lifestyle, or health factors were controlled. Treatment strategies that target depression should screen for hearing loss and bothersome tinnitus and provide management options for the conditions.
Evaluating Fixed Single-Point Parameters When Applied to Vestibular Evoked Myogenic Potentials: The Effect of Single Point and Signal Window
Authors: Romero Daniel J. , Clinard Christopher , Zalewski Christopher , Piker Erin
Published: January 2024

Objectives:

Several studies have applied a common objective detection algorithm (fixed single point [F
sp]) for detection of the vestibular evoked myogenic potential (VEMP). However, fundamental parameters of F
sp, such as establishing the location and duration of a signal window, have not been examined. In addition, F
sp criterion values used for response detection have not been established for cervical VEMPs (cVEMPs) or ocular VEMPs (oVEMPs). The purpose of this article was to investigate the effect of various single points and signal windows on F
sp, as well as determining F
sp criteria to determine response presence for cVEMP and oVEMP in a group of young healthy participants.

Design:

Twenty young healthy adults under the age of 30 and with no history of hearing or balance concerns were enrolled in the study protocol. Air-conducted cVEMPs and oVEMPs were evoked using 500 Hz tone bursts at 123 dB pSPL recorded at a fixed electromyography activation of 50 µV for cVEMPs and 35° gaze angle for oVEMPs. Responses were analyzed off-line using visual and objective detection. F
sp was applied to cVEMPs and oVEMPs using a range of single points and signal windows.

Results:

Noise variance was lowest for cVEMPs at the latency of P1, and for oVEMPs noise variance was not significantly different across the single-point latencies. On average, extending the length of the signal window lowered the F
sp value in cVEMPs and oVEMPs. An F
sp value of 2.0 was chosen as the criterion cutoff associated with the 95th percentile during no-response conditions using group data for cVEMPs and oVEMPs, respectively. F
sp values for cVEMPs and oVEMPs were not significantly different from each other.

Discussion:

This study established single-point latency and time-window parameters for VEMP-related applications of the F
sp detection algorithm. F
sp criteria values were established for cVEMP and oVEMP. Using these parameters, responses were detected in all participants.
Pharmacological Update and Emerging Treatments of Pulmonary Hypertension
Authors: Khan Shazli , Randhawa Sukhbir , Patail Haris , Spira Yaakov , Frishman William H. , Aronow Wilbert S. , Lanier Gregg M.
Published: January 2024

Pulmonary hypertension (PH) is defined as elevated pressures in the pulmonary artery and is associated with significant morbidity and mortality. The World Health Organization classifies PH into 5 distinct groups based on underlying etiology, pathology, and modality of treatment. Therapeutic approach may be challenging due to the extensive spectrum of causes and underlying mechanisms mediating PH. The 5 groups include pulmonary arterial hypertension (group 1), PH secondary to left heart disease (group 2), PH secondary to chronic lung disease (group 3), chronic thromboembolic pulmonary hypertension (group 4), and PH due to miscellaneous causes (group 5). Although significant progress has been made in the treatment of group 1 PH, there is a continued need to develop new therapies for all types of PH. Additionally, most treatments currently available improve functional capacity and symptoms but without a significant benefit in mortality. In this review, we aim to describe the various etiologies of PH and their established pharmacotherapies, as well as expand on emerging therapeutic options for each group.
Ideal frozen embryo transfer regime
Authors: Castillo Juan , Kol Shahar
Published: January 2024

Purpose of review

This review aims to compare evidence on four criteria (embryo implantation, obstetric outcomes, patient convenience, and IVF-unit efficiency) by analyzing published research on different endometrial preparation methods for frozen embryo transfer (FET).

Recent findings

While the artificial-FET cycle provides advantages in scheduling and implantation, it falls short in ensuring optimal obstetric outcomes. In contrast, natural-FET ensures embryo implantation conditions if ovulation is correctly identified. Supplementing with exogenous progesterone shields against low corpus luteum progesterone secretion, crucial for positive obstetric outcomes. In mNC-FET, ovulation is hCG-triggered, closely resembling natural cycles and reducing monitoring visits for enhanced patient convenience.

Letrozole is a recommended option for anovulatory patients, preserving endometrial thickness. It is cost-effective, less likely to induce multifollicular development than gonadotropins, and better tolerated.

In a novel approach, the natural-proliferative-phase-FET initiates progesterone in an unmediated ovulatory cycle at 7 mm endometrial thickness, combining the benefits of a natural proliferative endometrium with the convenience of scheduled artificial cycles.

The artificial cycle offers scheduling advantages, but may compromise obstetric outcomes. Natural FET relies on accurate ovulation timing for successful implantation. mNC-FET simplifies the process using hCG induction, minimizing clinic visits for improved convenience. Letrozole is highlighted as a cost-effective and well tolerated option in anovulatory patients. A recent innovative approach combines elements of natural and artificial cycles, showing promise for FET procedures.
Audiovestibular Findings in Patients with Concurrent Superior Canal Dehiscence and Vestibular Schwannoma
Authors: Tozzi Andrea , Castellucci Andrea , Ferrulli Giuseppe , Brandolini Cristina , Piras Gianluca , Martellucci Salvatore , Malara Pasquale , Ferri Gian Gaetano , Ghidini Angelo , Marchioni Daniele , Presutti Livio
Published: January 2024

Objective

To describe the clinical-instrumental findings in case of concurrent superior canal dehiscence (SCD) and ipsilateral vestibular schwannoma (VS), aiming to highlight the importance of an extensive instrumental assessment to achieve a correct diagnosis.

Study Design

Retrospective case review.

Setting

Tertiary referral center.

Patients

Five patients with concurrent SCD and VS.

Intervention

Clinical-instrumental assessment and imaging.

Main Outcome Measure

Clinical presentation, audiovestibular findings, and imaging.

Results

The chief complaints were hearing loss (HL) and unsteadiness (80%). Other main symptoms included tinnitus (60%) and pressure-induced vertigo (40%). Mixed-HL was identified in three patients and pure sensorineural-HL in 1, including a roll-over curve in speech-audiometry in two cases. Vibration-induced nystagmus was elicited in all cases, whereas vestibular-evoked myogenic potentials showed reduced thresholds and enhanced amplitudes on the affected side in three patients. Ipsilesional weakness on caloric testing was detected in three patients and a bilateral hyporeflexia in one. A global canal impairment was detected by the video-head impulse test in one case, whereas the rest of the cohort exhibited a reduced function for the affected superior canal, together with ipsilateral posterior canal impairment in two cases. All patients performed both temporal bones HRCT scan and brain-MRI showing unilateral SCD and ipsilateral VS, respectively. All patients were submitted to a wait-and-scan approach, requiring VS removal only in one case.

Conclusion

Simultaneous SCD and VS might result in subtle clinical presentation with puzzling lesion patterns. When unclear symptoms and signs occur, a complete audiovestibular assessment plays a key role to address imaging and diagnosis.
Timing of Kidney Replacement Therapy Initiation and Survival During Pediatric Extracorporeal Membrane Oxygenation: An Extracorporeal Life Support Organization Registry Study
Authors: Anton-Martin Pilar , Modem Vinai , Bridges Brian , Coronado Munoz Alvaro , Paden Matthew , Ray Meredith , Sandhu Hitesh S.
Published: January 2024

To characterize kidney replacement therapy (KRT) and pediatric extracorporeal membrane oxygenation (ECMO) outcomes and to identify the optimal timing of KRT initiation during ECMO associated with increased survival. Observational retrospective cohort study using the Extracorporeal Life Support Organization Registry database in children (0–18 yo) on ECMO from January 1, 2016, to December 31, 2020. Of the 14,318 ECMO runs analyzed, 26% of patients received KRT during ECMO. Patients requiring KRT before ECMO had increased mortality to ECMO decannulation (29% vs. 17%, OR 1.97, P < 0.001) and to hospital discharge (58% vs. 39%, OR 2.16, P < 0.001). Patients requiring KRT during ECMO had an increased mortality to ECMO decannulation (25% vs. 15%, OR 1.85, P < 0.001) and to hospital discharge (56% vs. 34%, OR 2.47, P < 0.001). Multivariable logistic regression demonstrated that the need for KRT during ECMO was an independent predictor for mortality to ECMO decannulation (OR 1.49, P < 0.001) and to hospital discharge (OR 2.02, P < 0.001). Patients initiated on KRT between 24 and 72 hours after cannulation were more likely to survive to ECMO decannulation and showed a trend towards survival to hospital discharge as compared to those initiated before 24 hours and after 72 hours.
The use of machine learning in paediatric nutrition
Authors: Young Aneurin , Johnson Mark J. , Beattie R. Mark
Published: January 2024

Purpose of review

In recent years, there has been a burgeoning interest in using machine learning methods. This has been accompanied by an expansion in the availability and ease of use of machine learning tools and an increase in the number of large, complex datasets which are suited to machine learning approaches. This review summarizes recent work in the field and sets expectations for its impact in the future.

Recent findings

Much work has focused on establishing good practices and ethical frameworks to guide the use of machine learning in research. Machine learning has an established role in identifying features in ‘omics’ research and is emerging as a tool to generate predictive models to identify people at risk of disease and patients at risk of complications. They have been used to identify risks for malnutrition and obesity. Machine learning techniques have also been used to develop smartphone apps to track behaviour and provide healthcare advice.

Machine learning techniques are reaching maturity and their impact on observational data analysis and behaviour change will come to fruition in the next 5 years. A set of standards and best practices are emerging and should be implemented by researchers and publishers.
Biologics, small molecule therapies and surgery in small bowel Crohn's disease
Authors: Steinberg Joshua M. , Chowdhury Reezwana , Sharma Sowmya , Charabaty Aline
Published: January 2024

Purpose of review

The terminal ileum and small bowel (SB) are involved in 30–45% of patients with Crohn's disease, while 20% have both small and large bowel involvement. Ileal Crohn's is associated with higher risk of progression to stricturing and penetrating disease1, hence it's imperative to utilize effective therapies to induce and maintain clinical and endoscopic remission and prevent intestinal complications. We review the available data of biologics and upadacitinib in small bowel disease, and the emerging data on the role of surgery as first line therapy for isolated Crohn's ileitis.

Recent findings

Most trials assessing drug efficacy do not report efficacy by disease location, and robust data on efficacy of therapies in isolated small bowel Crohn's is sparse. Several studies indicate that small bowel disease is generally less responsive to biologics, and could require higher drug trough levels to achieve endoscopic healing.

Current therapies for induction and maintenance of remission in moderate to severe Crohn's disease include several classes of monoclonal antibodies and a Janus Kinase inhibitor, upadacitinib. While small bowel Crohn's disease is generally less responsive to treatment, anti-TNFs are still preferred as first line therapy, and the option of early ileocecal resection in early limited ileal disease is gaining interest.
Postoperative small bowel Crohn's disease: how to diagnose, manage and treat
Authors: Ip Chak Lam , Boyapati Ray , Kalla Rahul
Published: January 2024

Purpose of review

Crohn's disease is a relapsing inflammatory condition and disease recurrence after surgery is common. Significant variation in clinical practice remains despite progress in management of postoperative Crohn's disease. In this review, we summarise current management strategies and guidelines, unmet needs, and research progress in this field.

Recent findings

There has been real progress in risk stratifying individuals’ postsurgery and tailoring therapies based on their risk; this has been incorporated into current management guidelines in the USA, UK, and Europe. Furthermore, novel noninvasive monitoring tools such as intestinal ultrasound have shown high sensitivity and specificity at detecting disease recurrence and are an attractive point-of-care test. Recent studies are also investigating multiomic biomarkers to prognosticate postoperative Crohn's disease. However, given the heterogeneity within this condition, large multicentre clinical validation across all age groups is needed for clinical translation in the future.

Ongoing progress in research and the development of novel prognostic and noninvasive disease monitoring tools offers hope for personalised therapy tailored to individual recurrence risk in postoperative Crohn's disease.
Towards a Standardized Classification of the Hepatobiliary Manifestations in Cystic Fibrosis (CFHBI): A Joint ESPGHAN/NASPGHAN Position Paper
Authors: Bodewes Frank A.J.A. , Freeman Alvin Jay , Weymann Alexander , Debray Dominique , Scheers Isabelle , Verkade Henkjan J. , Narkewicz Michael R.
Published: January 2024

The broad spectrum of hepatobiliary involvement in cystic fibrosis (CF) has been commonly referred to as cystic fibrosis liver disease (CFLD). However, differences in the definitions of CFLD have led to variations in reported prevalence, incidence rates, and standardized recommendations for diagnosis and therapies.

Harmonizing the description of the spectrum of hepatobiliary involvement in all people with CF (pwCF) is deemed essential for providing a reliable account of the natural history, which in turn supports the development of meaningful clinical outcomes in patient care and research.

Recognizing this necessity, The European Society for Paediatric Gastroenterology Hepatology and Nutrition (ESPGHAN) and the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN) commissioned and tasked a committee to develop and propose a systematic classification of the CF hepatobiliary manifestations to increase uniformity, accuracy, and comparability for clinical, registry, and research purposes. This report describes the committee's combined expert position statement on hepatobiliary involvement in CF, which has been endorsed by NASPGHAN and ESPGHAN.

We recommend using CFHBI (Cystic Fibrosis Hepato‐Biliary Involvement) as the updated term to describe and classify all hepatobiliary manifestations in all pwCF. CFHBI encompasses the current extensive spectrum of phenotypical, clinical, or diagnostic expressions of liver involvement observed in pwCF. We present a schematic categorization of CFHBI, which may also be used to track and classify the changes and development of CFHBI in pwCF over time. The proposed classification for CFHBI is based on expert consensus and has not been validated for clinical practice and research purposes. Achieving validation should be an important aim for future research.
Focused Cardiac Ultrasound Diagnosis of Dilated Cardiomyopathy
Authors: Perera AG Nuwan D. , Noorbakhsh Kathleen A. , Marin Jennifer R. , Azhdam Devora B.
Published: January 2024

We report the case of a 6-year-old boy presenting to the emergency department after a syncopal event during a flu-like illness. Intermittent ventricular tachycardia was noted during Emergency Medical Services transport, and a focused cardiac ultrasound (FOCUS) in the emergency department revealed a dilated left ventricle and left atrium as well as severe global systolic dysfunction. Point-of-care ultrasound findings prompted expedited evaluation and management of this critically ill patient.
The Knotted Urethral Catheter—Description of a Novel Technique and Steps for Removal
Authors: Rampersad Barbara , Paul Joanne F.
Published: January 2024

The spontaneous intravesicular knotting of a feeding tube used for urethral catheterization is a rare but documented complication. The reported incidence in the world literature is 0.2 per 100,000, with only 40 cases reported. Removal of these intravesicular knots has been attempted in a number of ways, such as the use of a guide wire to untangle the knot, use of excess lubrication and traction with or without anesthetic, and percutaneous or open cystostomy. This cystoscopic technique for removal has not been previously described.

Based on our experience and published recommendations, we formulate an algorithm for removal. We outline steps for prevention and techniques from simple to complex, which can be used to remove knotted catheters.

Although a rare complication of catheterization in children, catheter knotting can be troublesome. Following the steps suggested in this algorithm may avoid the use of more invasive techniques for removal.
Risk Factors Affecting Clinical Outcomes of Low-risk Early-stage Human Papillomavirus–Associated Endocervical Adenocarcinoma Treated by Surgery Alone: Application of Silva Pattern
Authors: Bae Bong Kyung , Bae Hyunsik , Cho Won Kyung , Kim Byoung-Gie , Choi Chel Hun , Kim Tae-Joong , Lee Yoo-Young , Lee Jeong-Won , Kim Hyun-Soo , Park Won
Published: January 2024

This study aimed to report the clinical outcomes and risk factors for survival of patients with low-risk early-stage human papillomavirus–associated (HPVA) endocervical adenocarcinoma (EAC) treated with surgery alone. This retrospective study obtained the clinicopathological data of patients with early-stage HPVA EAC who underwent surgery between 2012 and 2018. The Silva pattern of invasion was determined by reviewing pathology slides. Locoregional recurrence-free survival (RFS), RFS, and overall survival were calculated, and the risk factors for survival were analyzed. One hundred seventeen patients with a median follow-up of 5.2 years (0.5–9.7 yr) were included. The most common histologic type was usual (94/117, 80.3%). The Silva pattern was A in 79 patients (67.5%), B in 30 (25.6%), and C in 8 (6.8%). The 5-year locoregional RFS, RFS, and overall survival rates were 92.4%, 87.8%, and 97.2%, respectively. The presence of intermediate-risk factors and Silva pattern C were significantly associated with worse survival. Based on these findings, patients were categorized into 2 groups: Group 1 (Silva pattern A or Silva pattern B without intermediate-risk factors) and Group 2 (Silva pattern B with intermediate-risk factors or Silva pattern C). Group 2 showed significantly worse outcomes than Group 1, including the 5-year locoregional RFS (98.6% vs 68.0%), RFS (96.4% vs 54.6%), and overall survival (100.0% vs 86.5%). In conclusion, surgery alone for early-stage HPVA EAC resulted in favorable outcomes. Consideration of the Silva pattern, in addition to well-known risk factors, could help in precise risk group stratification of low-risk, early-stage HPVA EAC.
A Mixed-Methods Analysis of Deception Detection by Neurodiverse Young Adults
Authors: Coburn Kelly L. , Miller Gillian N. , Martin Lucas A. , Kana Rajesh K.
Published: January 2024

Purpose:

Differences in social cognition between autistic and nonautistic people may put autistic people at greater risk of being deceived. To inform communication interventions related to deception, the purposes of this mixed-methods study were to examine the deception detection strategies used by young adults with varying levels of autistic traits and to explore whether those strategies differed between groups or in terms of accuracy.

Methods:

Fifty-one young adults with varying levels of autistic traits watched a series of videos. For each video, the participant judged whether the recorded speaker was truthful and gave the reasoning for their judgment. Inductive thematic analysis was used to identify themes in participants' stated reasons, which were used to quantitatively examine (1) between-group differences based on self-reported autistic traits and (2) theme-based differences in accuracy.

Results:

Thematic analysis of the open-ended responses yielded four major themes: subjective descriptions of the person, nonverbal communication, observable features of the response, and nebulous reasons. Statistical analyses indicated no significant group differences in frequency of use of the four themes. When the four themes were compared with each other, observable response features yielded significantly more accurate judgments than nonverbal communication or subjective descriptions.

Discussion:

Findings are discussed within the framework of speech–language pathologists' role in helping communicators determine a speaker's truthfulness, with the ultimate goal of avoiding deception and/or manipulation. Suggestions for incorporating research findings into the design of communication interventions are included.
Thomas Wilson Meade. 21 January 1936—24 October 2022
Authors: Haines Sir Andy
Published: January 2024

Tom Meade made outstanding contributions to our understanding of the role of the haemostatic (clotting) system in the causation of cardiovascular disease by combining epidemiological approaches with rigorous standardization of laboratory methods. As director of the MRC Epidemiology and Medical Care Unit (EMCU) at Northwick Park Hospital he led major prospective studies to investigate the relationship between a range of haemostatic factors and cardiovascular disease outcomes. He also led several major randomized trials of interventions to reduce cardiovascular risk, notably the Thrombosis Prevention Trial. The EMCU also undertook several landmark studies on common and often neglected conditions to improve knowledge of the burden of ill health (for example from incontinence) and effective interventions, including for low back pain and stroke rehabilitation. In his later career he also set up and led a series of large case–control studies among myocardial infarction, stroke, deep vein thrombosis and pulmonary embolism cases, together with their matched controls using a primary care database, showing elevated risks of both arterial and venous thrombosis following respiratory infections. He had many major scientific leadership roles, including playing a significant role in guiding the UK Biobank at its inception and chairing the steering committee of the Heart Protection Study Collaborative Group.
Implementing measurement error models with mechanistic mathematical models in a likelihood-based framework for estimation, identifiability analysis and prediction in the life sciences
Authors: Murphy Ryan J. , Maclaren Oliver J. , Simpson Matthew J.
Published: January 2024

Throughout the life sciences, we routinely seek to interpret measurements and observations using parametrized mechanistic mathematical models. A fundamental and often overlooked choice in this approach involves relating the solution of a mathematical model with noisy and incomplete measurement data. This is often achieved by assuming that the data are noisy measurements of the solution of a deterministic mathematical model, and that measurement errors are additive and normally distributed. While this assumption of additive Gaussian noise is extremely common and simple to implement and interpret, it is often unjustified and can lead to poor parameter estimates and non-physical predictions. One way to overcome this challenge is to implement a different measurement error model. In this review, we demonstrate how to implement a range of measurement error models in a likelihood-based framework for estimation, identifiability analysis and prediction, called profile-wise analysis. This frequentist approach to uncertainty quantification for mechanistic models leverages the profile likelihood for targeting parameters and understanding their influence on predictions. Case studies, motivated by simple caricature models routinely used in systems biology and mathematical biology literature, illustrate how the same ideas apply to different types of mathematical models. Open-source Julia code to reproduce results is available on GitHub.
Deficiency of the ribosomal protein uS10 (RPS20) reorganizes human cells translatome according to the abundance, CDS length and GC content of mRNAs
Authors: Tian Yueming , Babaylova Elena S. , Gopanenko Alexander V. , Tupikin Alexey E. , Kabilov Marsel R. , Malygin Alexey A.
Published: January 2024

Ribosomal protein uS10, a product of the
RPS20
gene, is an essential constituent of the small (40S) subunit of the human ribosome. Disruptive mutations in its gene are associated with a predisposition to hereditary colorectal carcinoma. Here, using HEK293T cells, we show that a deficiency of this protein leads to a decrease in the level of ribosomes (ribosomal shortage). RNA sequencing of the total and polysome-associated mRNA samples reveals hundreds of genes differentially expressed in the transcriptome (t)DEGs and translatome (p)DEGs under conditions of uS10 deficiency. We demonstrate that the (t)DEG and (p)DEG sets partially overlap, determine genes with altered translational efficiency (TE) and identify cellular processes affected by uS10 deficiency-induced ribosomal shortage. We reveal that translated mRNAs of upregulated (p)DEGs and genes with altered TE in uS10-deficient cells are generally more abundant and that their GC contents are significantly lower than those of the respective downregulated sets. We also observed that upregulated (p)DEGs have longer coding sequences. Based on our findings, we propose a combinatorial model describing the process of reorganization of mRNA translation under conditions of ribosomal shortage. Our results reveal rules according to which ribosomal shortage reorganizes the transcriptome and translatome repertoires of actively proliferating cells.
Is biomedical research self-correcting? Modelling insights on the persistence of spurious science
Authors: Grimes David Robert
Published: January 2024

The reality that volumes of published biomedical research are not reproducible is an increasingly recognized problem. Spurious results reduce trustworthiness of reported science, increasing research waste. While science should be self-correcting from a philosophical perspective, that in insolation yields no information on efforts required to nullify suspect findings or factors shaping how quickly science may be corrected. There is also a paucity of information on how perverse incentives in the publishing ecosystem favouring novel positive findings over null results shape the ability of published science to self-correct. Knowledge of factors shaping self-correction of science remain obscure, limiting our ability to mitigate harms. This modelling study introduces a simple model to capture dynamics of the publication ecosystem, exploring factors influencing research waste, trustworthiness, corrective effort and time to correction. Results from this work indicate that research waste and corrective effort are highly dependent on field-specific false positive rates and time delays to corrective results to spurious findings are propagated. The model also suggests conditions under which biomedical science is self-correcting and those under which publication of correctives alone cannot stem propagation of untrustworthy results. Finally, this work models a variety of potential mitigation strategies, including researcher- and publisher-driven interventions.
Comparison of pooled semen insemination and single colony insemination as sustainable honeybee breeding strategies
Authors: Du Manuel , Bernstein Richard , Hoppe Andreas
Published: January 2024

Instrumental insemination of honeybees allows for two opposing breeding strategies. In single colony insemination (SCI), all drones to inseminate a queen are taken from one colony. In pooled semen insemination (PSI), sperm of many genetically diverse drones is mixed and queens are fertilized from the resulting drone pool. While SCI allows for maximum pedigree control, proponents of PSI claim to reduce inbreeding and maintain genetic variance. Using stochastic simulation studies, we compared genetic progress and inbreeding rates in small honeybee populations under SCI and PSI. Four different selection criteria were covered: estimated breeding values (EBV), phenotypes, true breeding values (TBV) and random selection. Under EBV-based truncation selection, SCI yielded 9.0% to 44.4% higher genetic gain than PSI, but had vastly increased inbreeding rates. Under phenotypical or TBV selection, the gap between SCI and PSI in terms of genetic progress narrowed. Throughout, PSI yielded lower inbreeding rates than SCI, but the differences were only substantial under EBV truncation selection. As a result, PSI did not appear as a viable breeding strategy owing to its incompatibility with modern methods of genetic evaluation. Instead, SCI is to be preferred but instead of strict truncation selection, strategies to avoid inbreeding need to be installed.
Direct method to determine singular point of enveloped surface and its application to worm wheel tooth surface
Authors: Cui Jian , Zhao Yaping , Meng Qingxiang , Li Gongfa
Published: January 2024

A novel methodology for determining the singular point of an enveloped surface is put forward. Unlike some existing methods, the presented method starts directly from the equation of the enveloped surface instead of that of the generating surface, and it is thus called a direct method. The calculation for the normal vector of the enveloped surface is well simplified with the help of the moving frame approach, which makes the presented method feasible. The singularity condition equation is extracted by using the theory of linear algebra. For singular points with different properties, proper solving techniques are established, including resultant elimination and simple elimination. Applying the developed method, the undercutting characteristics of the Archimedes worm wheel are investigated from the perspective of spatial meshing. The numerical results demonstrate that the worm wheel generally has one undercutting limit line, whose trend is along the tooth width of the wheel. Locating on one side of the tooth surface and near the tooth root is a dangerous part of the worm wheel undercutting. The proposed method is beneficial for the development of gear meshing science.
Pathogen detection in childhood exacerbated asthma in Sri Lanka, role and characteristics of Mycoplasma pneumoniae and antibiotic stewardship
Authors: Wijesooriya Lakmini Inoka , Chalker Victoria , Perera Priyantha , Sunil-Chandra N.P.
Published: January 2024

Abstract
Asthma is a significant public health concern, particularly in children. Exacerbation of asthma (EOA) is life-threatening and respiratory infections (RIs) play a crucial role. Though viruses play a significant role in EOA,  patients are empirically treated with antibiotics; in particular, macrolides are prescribed for unconfirmed M. pneumoniae infections. Although EOA and M. pneumoniae have been reported in many countries, no published data in Sri Lanka. The present study aimed to identify common respiratory viruses, typical respiratory bacterial pathogens, and M. pneumoniae in children with EOA   and relate them with the compatibility of antimicrobial use.
A case-control study was conducted in the pediatric unit of North Colombo Teaching Hospital, Sri Lanka, involving two groups of children between 5-15 years. Group-1: children with EOA, Group-2: children with stable asthma (SA). Each group consisted of 100 children. Sputum/throat swabs were tested for common respiratory viruses using specific  fluoresceinated monoclonal antibodies (MAbs) with  direct immunofluorescent staining, typical bacterial pathogens by routine culture and M. pneumoniae by RT-PCR. Macrolide-resistance in M. pneumoniae was detected using conventional PCR and sequencing for specific genetic mutations in the 23S rRNA gene. M. pneumoniae was genotyped using nested multilocus sequence typing (MLST), which targeted eight housekeeping genes  (ppa, pgm, gyrB, gmk, glyA, atpA, arcC, adk).
There was no significant difference in demographic data between the two groups. There was no statistically significant difference in age gender and geographical location between the two groups. In children with EOA, antibiotics were used in 66%, and macrolides in 42%. Samples consisted of 78%  sputum and 22% throat swabs. Adenovirus virus was the most common respiratory virus identified, and it was significantly higher in children with EOA compared to those with SA, but no significant difference in typical bacteria findings between the two groups.   M. pneumoniae was detected in one patient    in the group of 100 children with EOA with none  detected in the SA group. The  M. pneumoniae was macrolide sensitive, and as per MLST analysis, it was ST14. The empiric use of antibiotics in children with asthma may be better targeted with pathogen screening to inform treatment to minimize antibiotic resistance.