bluuebunny/crossref_metadata_2025 huggingface dataset:
What Is the Rate of Displacement of Occult Posterior Malleolus Fractures in Nailed Tibial Shaft Fractures?
Authors: Schiedo Ryan , Jo Jacob , Marin Arden , Fredette Ryan , Thomas Ayush , Siegel Jodi , Swart Eric
Published: June 2022

Objective:

To describe the radiographic consequences of posterior malleolus fractures (PMF) present with tibial shaft fractures fixed with intramedullary nails.

Design:

Retrospective cohort study.

Setting:

Level 1 trauma center.

Patients/Participants:

Seven hundred thirty-three patients with tibial shaft fractures.

Intervention:

Intramedullary nail fixation and prophylactic articular fixation.

Main Outcome Measure:

Displacement of PMF with intramedullary nail insertion.

Results:

Seven hundred thirty-three patients were identified with tibial shaft fractures treated with intramedullary nail fixation at a Level 1 trauma center without a uniform preoperative computed tomography protocol. One hundred thirty-three patients had an identifiable PMF appreciated on preoperative imaging. Of the 600 remaining patients without a known PMF, 29 had PMF identified after nail insertion: 24 patients with nondisplaced fractures that all healed radiographically at final follow-up, 3 patients had fractures <30% of the articular surface displaced 1–2 mm, and 2 patients had fractures >30% of the joint surface that displaced 1–2 mm.

Conclusions:

The incidence of radiographically observable PMF associated with tibial shaft fractures is high, even without a preoperative computed tomography screening protocol in place. In patients without an appreciable PMF on injury films, less than 1% (2/600) had displacement of a large, clinically significant PMF with nail placement.

Level of Evidence:

Prognostic Level IV. See Instructions for Authors for a complete description of levels of evidence.
The Effects of Liposomal Bupivacaine on Long-term Outcomes and Decreasing Immediate Postoperative Opioid Use Following One-level and Two-level Posterior Lumbar Fusions
Authors: Gannon Emmett , Freeman Matthew , Cornett Chris , Vincent Scott , Powers Sydney , Lyden Elizabeth
Published: June 2022

Study Design:

This is a retrospective observational study.

Objective:

This study aims to determine the efficacy of liposomal bupivacaine in postoperative analgesia and long-term outcomes in patients undergoing one-level and two-level posterior lumbar fusion.

Summary of Background Data:

Multiple studies have investigated the use of liposomal bupivacaine in spine surgery with varying results. The potential benefits of its use include decreasing postoperative opioid use, improved pain control, and a shorter hospital stay. Several studies have supported its use in spine surgery with others showing minimal to no benefit. No studies have investigated its possible impact on long-term outcomes.

Materials and Methods:

A total of 42 patients (22 one-level, 20 two-level) received liposomal bupivacaine injection just before surgical closure and were compared with a historical control group of 42 patients (27 one-level, 15 two-level) that did not receive liposomal bupivacaine. Daily opioid consumption was collected and converted to oral morphine equivalents. Length of stay and daily average pain scores using the visual analog scale were also recorded. In addition, SF-36 bodily pain and physical function outcome measures were collected preoperatively and at 6 months, 1 year and 2 years postoperatively.

Results:

The liposomal bupivacaine group was found to have a significantly lower total opioid consumption compared with the control group (P=0.001). The liposomal bupivacaine group was also found to use significantly fewer opioids on the day of surgery compared with the control group (P<0.0001). There was no significant difference shown in the average visual analog scale pain scores, length of stay, or long-term outcomes between the 2 groups.

Conclusions:

The use of liposomal bupivacaine in one-level and two-level posterior lumbar fusions shows promise as an adjuvant for postoperative analgesia by decreasing postoperative opioid consumption. With the varying results demonstrated with the utilization of liposomal bupivacaine in spine surgery, further investigation is warranted, namely a larger prospective randomized control study.

Level of Evidence:

Level III.
Centering the Patient in Postpartum Contraceptive Counseling
Authors: THOMPSON IVANA , BRYANT AMY G. , STUEBE ALISON M.
Published: June 2022

Birth control has long been considered an essential part of postpartum rounds. Many health care providers believe prevention of pregnancy is a priority in the postpartum period and that the inpatient postpartum stay is an ideal time to discuss contraception. This belief is not necessarily shared by birthing people. Many patients are unready to talk about contraception hours after birth, and contraceptive counseling may feel punitive for people whose reproduction has been marginalized. Health care providers must acknowledge this harmful and racist history to change counseling practices actively and thoughtfully to best meet patient needs while simultaneously respecting patient autonomy.
Management of Breast Cancer Survivors by Gynecologists
Authors: HUBER-KEENER KATHRYN J.
Published: June 2022

Breast cancer patients commonly present to their OBGYN during the process of diagnosis and treatment of breast cancer both for specific gynecologic needs and for primary care follow up. These patients require counseling on contraception, hormone use, and fertility at diagnosis. During treatment and survivorship, patients will face a variety of side effects from treatments leading to vasomotor symptoms, vulvovaginal discomfort, sexual dysfunction, osteoporosis, and vaginal bleeding. This chapters aims to enlighten providers on the unique range of issues a gynecologist may face when caring for breast cancer patients.
A Trauma-informed Approach to Postpartum Care
Authors: White Amina , Saxer Karen , Raja Sheela , Hall Sue L.
Published: June 2022

Distressing or traumatic perinatal experiences and adverse health outcomes can lead to particularly challenging postpartum experiences for patients and families. By adopting a trauma-informed care approach, the health care team can provide much-needed support, prevent additional harm, and promote healing. We propose practical communication, behavioral, and procedural considerations for integrating trauma-informed care principles into routine postpartum care, with attention to populations that have been marginalized. We see postpartum care as a critical component of holistic patient recovery and an opportunity to facilitate posttraumatic growth so that all families can thrive.
Cuffless blood pressure measuring devices: review and statement by the European Society of Hypertension Working Group on Blood Pressure Monitoring and Cardiovascular Variability
Authors: Stergiou George S. , Mukkamala Ramakrishna , Avolio Alberto , Kyriakoulis Konstantinos G. , Mieke Stephan , Murray Alan , Parati Gianfranco , Schutte Aletta E. , Sharman James E. , Asmar Roland , McManus Richard J. , Asayama Kei , De La Sierra Alejandro , Head Geoffrey , Kario Kazuomi , Kollias Anastasios , Myers Martin , Niiranen Teemu , Ohkubo Takayoshi , Wang Jiguang , Wuerzner Grégoire , O’Brien Eoin , Kreutz Reinhold , Palatini Paolo
Published: June 2022

Background:

Many cuffless blood pressure (BP) measuring devices are currently on the market claiming that they provide accurate BP measurements. These technologies have considerable potential to improve the awareness, treatment, and management of hypertension. However, recent guidelines by the European Society of Hypertension do not recommend cuffless devices for the diagnosis and management of hypertension.

Objective:

This statement by the European Society of Hypertension Working Group on BP Monitoring and Cardiovascular Variability presents the types of cuffless BP technologies, issues in their validation, and recommendations for clinical practice.

Statements:

Cuffless BP monitors constitute a wide and heterogeneous group of novel technologies and devices with different intended uses. Cuffless BP devices have specific accuracy issues, which render the established validation protocols for cuff BP devices inadequate for their validation. In 2014, the Institute of Electrical and Electronics Engineers published a standard for the validation of cuffless BP devices, and the International Organization for Standardization is currently developing another standard. The validation of cuffless devices should address issues related to the need of individual cuff calibration, the stability of measurements post calibration, the ability to track BP changes, and the implementation of machine learning technology. Clinical field investigations may also be considered and issues regarding the clinical implementation of cuffless BP readings should be investigated.

Conclusion:

Cuffless BP devices have considerable potential for changing the diagnosis and management of hypertension. However, fundamental questions regarding their accuracy, performance, and implementation need to be carefully addressed before they can be recommended for clinical use.
Exploring Alternate Visions of Caring in a World of Social Distancing
Authors: Long Elizabeth M. , Knight Stacey L.
Published: June 2022

Compounded by the COVID-19 pandemic, both loneliness and isolation are a growing concern for the older adult population. An intergenerational holistic exchange, Cardinals CARE (Cardinals, Adopt, Residents for Engagement), was developed as a way to connect older adults in long-term care facilities (LTCFs) with nursing students while demonstrating the meeting of student service learning outcomes. Students shared correspondence with residents in LTCFs for a 10-week period, sending mail weekly in the form of letters, artwork, crafts, an appropriate joke, or anything to encourage engagement. Jean Watson's Theory of Transpersonal Caring was used as a framework for the project. Students (n = 109) participating in the program provided interaction with 734 residents in 11 LTCFs in 3 counties. Students utilized reflective journaling to demonstrate the meeting of service learning outcomes and described the power of connection and the opportunity to provide holistic care. A result of the project was the intergenerational connectedness showcasing the reciprocal nature of the CARE project. Further research is needed to build an evidence base for the use of such interaction to promote connection and combat loneliness.
The Effect of Lavender on Sleep Quality in Individuals Without Insomnia
Authors: Chen Tzu-Ying , Hiyama Akiko , Muramatsu Masumi , Hinotsu Atsuko
Published: June 2022

We reviewed 20 randomized controlled trials concerning the intervention methods and effects of lavender essential oil on adults' sleep quality. Fourteen showed positive intervention effects. A mixture of subjective and objective indicators was used. Lavender essential oil was associated with improved sleep quality before insomnia or other sleep disorders occurred.
Gonadal hormone–dependent nociceptor sensitization maintains nociplastic pain state in female mice
Authors: Hankerd Kali , Koo Ho , McDonough Kathleen E. , Wang Jigong , Pariyar Ramesh , Tang Shao-Jun , Chung Jin Mo , La Jun-Ho
Published: June 2022

Nociplastic pain conditions develop predominantly in women. We recently established a murine nociplastic pain model by applying postinjury thermal (40°C) stimulation to an injured (capsaicin-injected) area, triggering a transition to a nociplastic pain state manifesting as persistent mechanical hypersensitivity outside of the previously injured area. The nociplastic pain state was centrally maintained by spinal microglia in males but peripherally by ongoing afferent activity at the previously injured area in females. Here, we investigated whether gonadal hormones are critical for the development of this peripherally maintained nociplastic pain state in females. Although the transition to a nociplastic pain state still occurred in ovariectomized females, the pain state was maintained neither by ongoing afferent activity at the previously injured area nor by spinal microglia. Estradiol reconstitution a week before the injury plus postinjury stimulation, but not after the transition had already occurred, restored the development of peripherally maintained nociplastic mechanical hypersensitivity in ovariectomized females. G protein–coupled estrogen receptor antagonism during the transition phase mimicked ovariectomy in gonad-intact females, whereas the receptor antagonism after the transition gradually alleviated the nociplastic mechanical hypersensitivity. At the previously injured area, afferents responsive to allyl isothiocyanate (AITC), a TRPA1 agonist, contributed to the maintenance of nociplastic mechanical hypersensitivity in gonad-intact females. In ex vivo skin-nerve preparations, only AITC-responsive afferents from the nociplastic pain model in gonad-intact females showed ongoing activities greater than control. These results suggest that gonadal hormones are critical for peripherally maintained nociplastic pain state in females by sensitizing AITC-responsive afferents to be persistently active.
Dietary Beliefs in Children and Adolescents with Inflammatory Bowel Disease and their Parents
Authors: Bramuzzo Matteo , Grazian Federica , Grigoletto Veronica , Daidone Alessandro , Martelossi Stefano , Mario Federica , Maurel Eleonora , Lega Sara , Giudici Fabiola , Di Leo Grazia , Barbi Egidio
Published: June 2022

Objectives:

Patients with inflammatory bowel disease (IBD) may have diet-related beliefs that lead to restrictive dietary behaviours. This study aimed to evaluate dietary beliefs in young patients with IBD and their parents and the presence of restrictive behaviours.

Methods:

A questionnaire regarding dietary beliefs was administered to IBD patients aged 8-17 years and their parents. A Food Frequency Questionnaire was administered to patients with IBD and a peer control group.

Results:

Seventy-five patients and 105 parents were interviewed. Twenty-seven (36%) patients and 39 (37.1%) parents believed that dietary modifications could control the IBD course.

Twenty-five (33.0%) patients and 33 (33.0%) parents believe that some dietary components can prevent relapse or improve symptoms (mainly abdominal pain and diarrhoea), while 36 (48%) patients and 60 (60.0%) parents believe that some foods can induce or worsen symptoms during an IBD flare.

Patients believe that milk, dairy, fried and spicy foods, sweets and carbonated drinks could have a negative effect on IBD while fruits, vegetables and rice could have a positive impact. Parents believe that fruits and vegetables have a negative effect.

Responses did not differ among patients classified according to IBD phenotype, activity status, or current therapies.

Compared to controls, young patients with IBD have reduced daily consumption of milk, lunch meat, raw and cooked vegetables.

Conclusions:

About one-third of paediatric patients with IBD and their parents have dietary beliefs that lead to restrictive dietary behaviours.
Clinical exome sequencing for stroke evaluation uncovers a high frequency of Mendelian disorders: a retrospective analysis
Authors: Kumar Runjun D. , Meng Linyan , Liu Pengfei , Miyake Christina Y. , Worley Kim C. , Bi Weimin , Lalani Seema R.
Published: June 2022

Background

Stroke causes significant disability and is a common cause of death worldwide. Previous studies have estimated that 1-5% of stroke is attributable to monogenic etiologies. We set out to assess the utility of clinical exome sequencing (ES) in the evaluation of stroke.

Methods

We retrospectively analyzed 124 individuals who received ES at the Baylor Genetics reference lab between 2012 and 2021 who had stroke as a major part of their reported phenotype.

Results

Ages ranged from 10 days to 69 years. 8.9% of the cohort received a diagnosis, including 25% of infants less than 1 year old; an additional 10.5% of the cohort received a probable diagnosis. We identified several syndromes that predispose to stroke such asCOL4A1-related brain small vessel disease,CBS-related homocystinuria,POLG-related disorders,TTC19-related mitochondrial disease, andRNASEH2Aassociated Aicardi-Goutieres syndrome. We also observed pathogenic variants inNSD1, PKHD1, HRASandATP13A2, which are genes rarely associated with stroke.

Conclusions

Although stroke is a complex phenotype with varying pathologies and risk factors, these results show that use of exome sequencing can be highly relevant in stroke, especially for those presenting <1 year of age.
Genetic association analysis of 269 rare diseases reveals novel aetiologies
Authors: Greene Daniel ,   Genomics England Research Consortium, Pirri Daniela , Frudd Karen , Sackey Ege , Al-Owain Mohammed , Giese Arnaud P.J. , Ramzan Khushnooda , Yamanaka Itaru , Boeckx Nele , Thys Chantal , Gelb Bruce D. , Brennan Paul , Hartill Verity , Harvengt Julie , Kosho Tomoki , Mansour Sahar , Masuno Mitsuo , Ohata Takako , Stewart Helen , Taibah Khalid , Turner Claire L.S. , Imtiaz Faiqa , Riazuddin Saima , Morisaki Takayuki , Ostergaard Pia , Loeys Bart , Morisaki Hiroko , Ahmed Zubair M. , Birdsey Graeme M. , Freson Kathleen , Mumford Andrew , Turro Ernest
Published: June 2022

The genetic aetiologies of more than half of rare diseases remain unknown1. Standardised genome sequencing (GS) and phenotyping of large patient cohorts provides an opportunity for discovering the unknown aetiologies2, but this depends on efficient and powerful analytical methods3. We have developed a portable computational and statistical framework for inferring genetic associations with rare diseases. At its core lies the ‘Rareservoir’, a compact database of rare variant genotypes and phenotypes. We built a Rareservoir of 77,539 genomes sequenced by the 100,000 Genomes Project (100KGP)4. We then applied the Bayesian association method, BeviMed3, across 269 rare diseases assigned to participants in the project, identifying 238 known5and 21 novel associations. The novel results included three which we selected for validation. We provide compelling evidence that (1) loss-of-function variants in the ETS-family transcription factor encoding geneERGlead to primary lymphoedema, (2) truncating variants in the last exon of TGFβ regulatorPMEPA1result in Loeys-Dietz syndrome6, and (3) loss-of-function variants inGPR156give rise to recessive congenital hearing impairment. These novel findings confirm the power of our analytical approach for the aetiological discovery of rare diseases.
Context- and scale-dependent effects of thymol bioactivity on biological networks: contributions from quail under heat stress
Authors: Fernandez Maria Emilia , Bonansea Rocío Inés , Mas Agustin Lucini , Baroni María Verónica , Marin Raul Hector , Labaque Maria Carla , Kembro Jackelyn M.
Published: June 2022

A defining feature of healthy function is adaptability, the capacity to dynamically respond to novel and/or unpredictable factors, such as exposition to environmental challenges. Here we explore the role of context (i.e., order in which factors are applied) on the configuration of networks of behavioral and physiological traits from Japanese quail that were supplemented dietary thymol prior, jointly or after onset of a chronic heat stress protocol (i.e., supplementation strategies). Basal diet and standard environmental temperature were used as controls. We begin by showing that each supplementation strategy evolved differently over the 5-week experimental period in regard to body weight and feed- intake. At the end of this experimental period, context-dependency was also observed in the non- trivial functional relationships among 27 traits from 4 subsystems from distinct spatial-temporal scales. When considered separately, whole-organism level subsystems (i.e. somatic maintenance and egg production traits), are predominantly functionally related to environmental temperature. Conversely, at the molecular level, the liveŕs antioxidant system response is fundamentally dominated by the supplementation strategy. Interestingly, the serum’s antioxidant system shows an intermediate response, not dominated by a given factor. Overall, network configurations were highly dependent on context, and could be associated with specific induced physiological states. Our work constitutes the first study that includes network, integrative, and experimentally comparative analyses applied to the field of dietary supplementation under environmental challenges. This perspective could help understand complex biological responses important for developing efficient and welfare orientated supplementation protocols for farm animals and for interpreting the background in this field.
Exome-wide association studies discover germline mutation patterns and identify high-risk populations in human cancers
Authors: Shen Sipeng , Jiang Yunke , Wang Guanrong , Li Hongru , You Dongfang , Duan Weiwei , Zhang Ruyang , Wei Yongyue , Shen Hongbing , Hu Zhibin , Christiani David C. , Zhao Yang , Chen Feng
Published: June 2022

Genome-wide association studies have discovered numerous common variants associated with human cancers. However, the contribution of exome-wide rare variants to cancers remains largely unexplored, especially for the protein-coding variants. The UK Biobank provides detailed cancer follow-up information linked to whole-exome sequencing (WES) for approximately 450,000 participants, offering an unprecedented opportunity to evaluate the effect of exome variation on pan-cancer. Here, we performed exome-wide association studies (ExWAS) based on single variant levels and gene levels to detect their associations across 20 primary cancer types in the discovery set (WES-300k, N = 284,456) and replication set (WES-150k, N = 143,478), separately. The ExWAS detected 143 independent variants at variant-level and 49 genes at gene-level, while nine variants and eight genes were shared across cancers. In the cross-trait meta-analysis, we identified 239 additional independent pleiotropic variants, mapping to the genes which were functional through trans-omics analyses in transcriptomics and proteomics. Further, we developed exome-wide risk scores (ERS) to identify high-risk populations based on rare variants with minor allele frequency (MAF) < 0.05. The ERS had satisfactory performance in cancer risk stratification, especially for the extremely high-risk persons (top 5% ERS) that were frequently risk allele carriers. The ERS (median C-index (IQR): 0.655 (0.636-0.667)) outperforms the traditional polygenic risk score (PRS) (median C-index (IQR): 0.585 (0.572-0.614)) for discrimination in the replication set. Our findings offer further insight into the genetic architecture of human exomes for cancer susceptibility.
Genetic risk, parental history, and suicide attempts in a diverse sample of US adolescents
Authors: Barzilay Ran , Visoki Elina , Schultz Laura M , Warrier Varun , Daskalakis Nikolaos P , Almasy Laura
Published: June 2022

Background

Adolescent suicide is a major health problem in the US marked by a recent increase in Black/African American youth suicide trends. While genetic factors partly account for familial transmission of suicidal behavior, it is not clear whether polygenic risk scores of suicide attempt have clinical utility in youth suicide risk classification.

Objectives

To evaluate the contribution of a polygenic risk score for suicide attempt (PRS-SA) in explaining variance in suicide attempt by early adolescence.

Methods

We studied N=5,214 non-related Black and White youth from the Adolescent Brain Cognitive Development (ABCD) Study (ages 8.9-13.8 years) who were evaluated between 2016 and 2021. Regression models tested associations between PRS-SA and parental history of suicide attempt/death with youth-reported suicide attempt. Covariates included age, sex, and race.

Results

Over three waves of assessments, 182 youth (3.5%) reported a past suicide attempt, with Black youth reporting significantly more suicide attempts than their White counterparts (6.1% vs 2.8%, P<.001). PRS-SA was associated with suicide attempt (odds ratio [OR]=1.3, 95% confidence interval [CI] 1.1-1.5, P=.001). Inclusion of PRS-SA explained 2.7% of the variance in suicide attempts, significantly more than the base model including only age, sex and race, which explained 1.9% of the variance (P=.001). Parental history of suicide attempt/death was also associated with youth suicide attempt (OR=2.9, 95%CI 1.9-4.4, P<.001). Addition of PRS-SA to the model that included parental history significantly increased the variance explained from 3.3% to 4% (P=.002).

Conclusions

Findings suggest that PRS-SA may be useful for suicide risk classification in diverse youth.

Contribution to the Field Statement

Adolescent suicidal behavior is a major health problem, with suicide being the 2nd leading cause of death in youth. Research that improves our understanding regarding drivers of suicide risk in youth can inform youth suicide prevention strategies. Family history of suicide is an established risk factor for youth suicidal behavior. Current methods in psychiatric genetics allow calculation of polygenic risk scores that represent genetic liability to specific conditions. It is not clear whether polygenic risk score of suicide attempt can assist in risk classification, beyond family history. In this work, we show that in a sample of 5,214 youth ages 9-13, of which 3.5% reported past suicide attempt, polygenic score of suicide attempt was associated with youth suicide attempt. This association additively explained variance over and above parental history of suicide attempt/death. Findings make a case for the potential utility of incorporating polygenic risk scores as part of suicide attempt risk classification in youth, and suggest that polygenic scores may reveal genetic liability that is not captured by family history of suicide.
Rapid Response for Notification of Monkeypox Exposure, Exposure Risk Assessment and Stratification, and Symptom Monitoring
Authors: Simpson Lynn A. , Macdonald Kaitlin , Searle Eileen F. , Shearer Jennifer A. , Dimitrov Dimitar , Foley Daniel , Morales Eduardo , Shenoy Erica S.
Published: June 2022

Objective

Public health authorities recommend symptom monitoring of healthcare personnel (HCP) after defined exposures to Monkeypox (MPX). We report on the rapid development and implementation of mobile responsive survey solutions for notification of possible exposure, exposure risk assessment and stratification, and symptom monitoring.

Setting

Academic health center in Boston, Massachusetts, after admission of first diagnosed case of MPX in the United States during the current global outbreak.

Participants

Research Electronic Data Capture (REDCap) design and programmers, Infection Control, Occupational Health, and Emergency Preparedness specialists, and HCP with possible exposure to MPX.

Interventions

Design and deployment of Research Electronic Data Capture (REDCap) tools to identify HCP with possible exposure to MPX, perform exposure risk assessment and stratification for post-exposure prophylaxis (PEP), and conduct symptom monitoring during the exposure window. Project enhancements included dashboards for HCP tracking and SMS text reminders for symptom monitoring.

Results

Tools to support the contact tracing and exposure investigation were deployed within 24 hours of identification of a patient with suspected MPX, with the full suite in production within 4 days of confirmation of the diagnosis of MPX. Clinical follow up of HCP was integrated into the design, and real-time versioning allowed for adjustments leading to improvements in HCP symptom monitoring compliance and enhanced tracking.

Conclusions

During the current MPX outbreak, timely and comprehensive evaluation of potential HCP exposures is necessary but presents logistical challenges. Rapid development of MPX-specific solutions using REDCap enabled flexibility in design and approach, and integration of targeted clinical support enhanced functionality.
Prevalence of COVID-19 and Long COVID in Collegiate Student Athletes from Spring 2020 to Fall 2021: A Retrospective Survey
Authors: Massey Daisy , Saydah Sharon , Adamson Blythe , Lincoln Andrew , Aukerman Douglas F. , Berke Ethan M. , Sikka Robby , Krumholz Harlan M.
Published: June 2022

Symptomatic COVID-19 and post-COVID conditions, also referred to as post-acute sequelae of SARS-CoV-2 (PASC) or Long COVID, have been widely reported in young, healthy people, but their prevalence has not yet been determined in student athletes. We surveyed a convenience sample of 18 collegiate school administrators, representing about 7,000 student athletes. According to their survey responses, 9.8% of student athletes tested positive for COVID-19 in spring 2020 and 25.4% tested positive in the academic year of fall 2020 to spring 2021. About 4% of student athletes who tested positive from spring 2020 to spring 2021 developed Long COVID, defined as new, recurring, or ongoing physical or mental health consequences occurring 4 or more weeks after SARS-CoV-2 infection. This study highlights that Long COVID occurs in healthy collegiate athletes and merits a larger study to determine population-wide prevalence.
A nomogram to predict failure rate in immediate implant-based breast reconstruction
Authors: Zhu Meizhen , Zhang Fanrong , Mao Jiefei , Fang Jun , Chen Daobao
Published: June 2022

Controversies on risk factors affecting immediate implant-based breast reconstruction (IBBR) still exist. We aimed to evaluate risk factors of reconstruction failure (RF) in immediate IBBR. We retrospectively reviewed 239 patients (241 breasts) who underwent immediate IBBR from 2011 to 2019. A nomogram was established to predict RF rate in stage I operation and logistic regression model was created for stage II operation. 14 (5.81%) and 7 (5.51%) reconstructive breasts experienced RF in stage I and II operation, respectively. Body mass index (BMI) [odds ratio (OR)=1.569, 95% confidence interval (CI): 1.087-2.263, p=0.016], implant/tissue expander (TE) volume>86.30% (OR=5.711, 95% CI: 1.067-30.583, p=0.042), adjuvant chemotherapy (ACT) (OR=30.094, 95% CI: 2.030-446.084, p=0.013) were independent risk factors for RF in stage I operation. The nomogram to predict RF rate in stage I operation revealed area under the curve (AUC) was 0.920 (95% CI: 0.844-0.995). Logistic regression demonstrated that mesh use was the independent predictor of RF in stage II operation (OR=47.326, 95% CI: 3.11-720.081, p=0.005). The nomogram exhibited satisfied predictive ability. Present findings enhanced our understanding of the risk factors contributing to RF and might lead us clinical decision to improve the outcome of immediate IBBR.
High-Coverage Four-Dimensional Data-Independent Acquisition Proteomics and Phosphoproteomics Enabled by Deep Learning-Driven Multi-Dimensional Prediction
Authors: Chen Moran , Zhu Pujia , Wu Pengfei , Hao Yanhong , Zhang Zhourui , Sun Jian , Nie Wenjing , Chen Suming
Published: June 2022

Four-dimensional (4D) data-independent acquisition (DIA)-based proteomics is an emerging technology that has been proven to have high precursor ion sampling efficiency and higher precursor identification specificity. However, the current 4D DIA proteomics is still dependent on the building of project-specific experimental library which is time-consuming and limits the coverage for identification/quantification. Herein, a workflow of 4D DIA proteomics by using the predicted multi-dimensional in silico library was established. A deep learning model Deep4D that could high-accurately predict the CCS and RT of both the unmodified and phosphorylated peptides was developed. By using an integrated 4D in silico library containing millions of peptides, we have identified 25% more protein than using experimental libraries in the DIA proteomics analysis of HeLa cells. We further demonstrate that the introduction of in silico prediction library can greatly complement the experimental library of directly obtained phosphorylated peptides, resulting in a greater increase in the identification of phosphorylated peptides and phosphorylated proteins.
Lowering of circulating sclerostin may increase risk of atherosclerosis and its risk factors: evidence from a genome-wide association meta-analysis followed by Mendelian randomization
Authors: Zheng Jie , Wheeler Eleanor , Pietzner Maik , Andlauer Till , Yau Michelle , Hartley April E. , Brumpton Ben Michael , Rasheed Humaira , Kemp John P , Frysz Monika , Robinson Jamie , Reppe Sjur , Prijatel Vid , Gautvik Kaare M , Falk Louise , Maerz Winfried , Gergei Ingrid , Peyser Patricia A , Kavousi Maryam , de Vries Paul S. , Miller Clint L. , Bos Maxime , van der Laan Sander W. , Malhotra Rajeev , Herrmann Markus , Scharnagl Hubert , Kleber Marcus , Dedoussis George , Zeggini Eleftheria , Nethander Maria , Ohlsson Claes , Lorentzon Mattias , Wareham Nick , Langenberg Claudia , Holmes Michael V. , Smith George Davey , Tobias Jonathan H.
Published: June 2022

Sclerostin inhibition is a new therapeutic approach for increasing bone mineral density (BMD) but its cardiovascular safety is unclear. We conducted a genome-wide association study (GWAS) meta-analysis of circulating sclerostin in 33,961 Europeans followed by Mendelian randomization (MR) to estimate the causal effects of sclerostin on 15 atherosclerosis-related diseases and risk factors. GWAS meta-analysis identified 18 variants independently associated with sclerostin, which including a novel cis signal in the SOST region and three trans signals in B4GALNT3, RIN3 and SERPINA1 regions that were associated with opposite effects on circulating sclerostin and eBMD. MR combining these four SNPs suggested lower sclerostin increased hypertension risk (odds ratio [OR]=1.09, 95%CI=1.04 to 1.15), whereas bi-directional analyses revealed little evidence for an effect of genetic liability to hypertension on sclerostin levels. MR restricted to cis (SOST) SNPs additionally suggested sclerostin inhibition increased risk of type 2 diabetes (T2DM) (OR=1.26; 95%CI=1.08 to 1.48) and myocardial infarction (MI) (OR=1.31, 95% CI=1.183 to 1.45). Furthermore, these analyses suggested sclerostin inhibition increased coronary artery calcification (CAC) (β=0.74, 95%CI=0.33 to 1.15), levels of apoB (β=0.07; 95%CI=0.04 to 0.10; this result was driven by rs4793023) and triglycerides (β=0.18; 95%CI=0.13 to 0.24), and reduced HDL-C (β=-0.14; 95%CI=-0.17 to -0.10). This study provides genetic evidence to support a causal effect of sclerostin inhibition on increased hypertension risk. Cis-only analyses suggested that sclerostin inhibition additionally increases the risk of T2DM, MI, CAC, and an atherogenic lipid profile. Together, our findings reinforce the requirement for strategies to mitigate against adverse effects of sclerostin inhibitors like romosozumab on atherosclerosis and its related risk factors.
Managing the evidence infodemic: Automation approaches used for developing NICE COVID-19 living guidelines
Authors: Sood Mariam , Sharp Steve , McFarlane Emma , Willans Robert , Hopkins Kathryn , Karpusheff Justine , Glen Fiona
Published: June 2022

Background and Objectives

The National Institute for Health and Care Excellence (NICE) produces evidence-based guidance and advice for health, public health and social care practitioners in England and Wales. Between March 2020 and March 2022, NICE produced 24 COVID-19 guidelines to support healthcare workers during the COVID-19 pandemic. This article outlines three automation strategies NICE utilised to facilitate faster processing of evidence on COVID-19 and describes the value of those approaches when there is an increasing volume of evidence and demand on resources.

Study Design and Setting

Text classification using machine learning, and regular expression-based pattern matching were used to automate screening of literature search results. Relevant clinical trials were tracked by automated monitoring of clinical trial databases and Pubmed.

Results

The strategies discussed here brought considerable efficiencies in the processing time without impacting on quality compared to equivalent manual efforts. Additionally, the paper illustrates how to incorporate automation into established processes of the evidence management pipeline.

Conclusions

We have demonstrated through testing and use in live guideline development and surveillance that these are effective and low risk approaches at managing high volumes of evidence.

Highlights

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To illustrate how NICE utilised automation to handle the Covid-19 ‘infodemic’-managing the ‘infodemic’ of evidence surveillance is a shared global issue.

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To outline automation strategies to facilitate faster processing of evidence, especially when there is an increasing volume of evidence and demand on resources.

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How automation can be included in established processes without disrupting business as usual operations.

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Automation can take many forms, and depending on risk appetite, can be supplemented with manual checking.

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Automation can be adopted easily with the right tools and techniques.
Variable-Selection ANOVA Simultaneous Component Analysis (VASCA)
Authors: Camacho José , Vitale Raffaele , Morales-Jimenez David , Gómez-Llorente Carolina
Published: June 2022

Motivation

ANOVA Simultaneous Component Analysis (ASCA) is a popular method for the analysis of multivariate data yielded by designed experiments. Meaningful associations between factors/interactions of the experimental design and measured variables in the data set are typically identified via significance testing, with permutation tests being the standard go-to choice. However, in settings with large numbers of variables, the “holistic” testing approach of ASCA (all variables considered) often overlooks statistically significant effects encoded by only a few variables.

Results

We propose Variable-selection ASCA (VASCA), a method that generalizes ASCA through variable selection, augmenting its statistical power without inflating the Type-I error risk. The method is evaluated with simulations and with a real data set from a multi-omic clinical experiment. We show that VASCA is more powerful than both ASCA and the widely-adopted False Discovery Rate (FDR) controlling procedure; the latter is used as a benchmark for variable selection based on multiple significance testing. We further illustrate the usefulness of VASCA for exploratory data analysis in comparison to the popular Partial Least Squares Discriminant Analysis (PLS-DA) method and its sparse counterpart (sPLS-DA).

Availability

The code for VASCA is available in the MEDA Toolbox athttps://github.com/josecamachop/MEDA-Toolbox

Contact

josecamacho@ugr.es

Supplementary information

Supplementary data are available atBioinformaticsonline.
Mitochondrial MICOS complex genes, implicated in hypoplastic left heart syndrome, maintain cardiac contractility and actomyosin integrity
Authors: Birker Katja , Kirkland Natalie J. , Theis Jeanne L. , Fogarty Zachary C. , Missinato Maria Azzurra , Kalvakuri Sreehari , Grossfeld Paul , Engler Adam J. , Ocorr Karen , Nelson Timothy J. , Colas Alexandre R. , Olson Timothy M. , Vogler Georg , Bodmer Rolf
Published: June 2022

Hypoplastic left heart syndrome (HLHS) is a severe congenital heart disease (CHD) with a likely oligogenic etiology, but our understanding of the genetic complexities and pathogenic mechanisms leading to HLHS is limited. We therefore performed whole genome sequencing (WGS) on a large cohort of HLHS patients and their families to identify candidate genes that were then tested in Drosophila heart model for functional and structural requirements. Bioinformatic analysis of WGS data from an index family comprised of a HLHS proband born to consanguineous parents and postulated to have a homozygous recessive disease etiology, prioritized 9 candidate genes with rare, predicted damaging homozygous variants. Of the candidate HLHS gene homologs tested, cardiac-specific knockdown (KD) of mitochondrial MICOS complex subunit dCHCHD3/6 resulted in drastically compromised heart contractility, diminished levels of sarcomeric actin and myosin, reduced cardiac ATP levels, and mitochondrial fission-fusion defects. Interestingly, these heart defects were similar to those inflicted by cardiac KD of ATP synthase subunits of the electron transport chain (ETC), consistent with the MICOS complex’s role in maintaining cristae morphology and ETC complex assembly. Analysis of 183 genomes of HLHS patient-parent trios revealed five additional HLHS probands with rare, predicted damaging variants in CHCHD3 or CHCHD6. Hypothesizing an oligogenic basis for HLHS, we tested 60 additional prioritized candidate genes in these cases for genetic interactions with CHCHD3/6 in sensitized fly hearts. Moderate KD of CHCHD3/6 in combination with Cdk12 (activator of RNA polymerase II), RNF149 (E3 ubiquitin ligase), or SPTBN1 (scaffolding protein) caused synergistic heart defects, suggesting the potential involvement of a diverse set of pathways in HLHS. Further elucidation of novel candidate genes and genetic interactions of potentially disease-contributing pathways is expected to lead to a better understanding of HLHS and other CHDs.
Both social environment and chronological age shape the physiology of ant workers
Authors: Quque Martin , Brun Charlotte , Villette Claire , Sueur Cédric , Criscuolo François , Heintz Dimitri , Bertile Fabrice
Published: June 2022

Position within the social group has consequences on individual lifespans in diverse taxa. This is especially obvious in eusocial insects, where workers differ in both the tasks they perform and their aging rates. However, in eusocial wasps, bees and ants, the performed task usually depends strongly on age. As such, untangling the effects of social role and age on worker physiology is a key step towards understanding the coevolution of sociality and aging. We performed an experimental protocol that allowed a separate analysis of these two factors using four groups of black garden ant (Lasius niger) workers: young foragers, old foragers, young nest workers, and old nest workers. We highlighted age-related differences in the proteome and metabolome of workers that were primarily related to worker subcaste and only secondarily to age. The relative abundance of proteins and metabolites suggests an improved xenobiotic detoxification, and a fuel metabolism based more on lipid use than carbohydrate use in young ants, regardless of their social role. Regardless of age, proteins related to the digestive function were more abundant in nest workers than in foragers. Old foragers were mostly characterized by weak abundances of molecules with an antibiotic activity or involved in chemical communication. Finally, our results suggest that even in tiny species, extended lifespan may require to mitigate cancer risks. This is consistent with results found in eusocial rodents and thus opens up the discussion of shared mechanisms among distant taxa and the influence of sociality on life history traits such as longevity.
Stagnation in quality of next-generation sequencing assays for the diagnosis of hereditary hematopoietic malignancies
Authors: Roloff Gregory W. , Shaw Reid , O’Connor Timothy E. , Drazer Michael W.
Published: June 2022

Importance

Hereditary hematopoietic malignancies (HHMs) are hereditary cancer syndromes that constitute at least 14% of all myeloid malignancies, but genetic assays used to diagnose HHMs have historically been of variable quality. Here, we demonstrate that HHM assays continue to have persistent shortcomings. These diagnostic gaps place patients with HHMs at high risk for missed diagnoses, missed opportunities for cancer screening, and donor-derived leukemias following stem cell transplant.

Objective

To determine if the quality of HHM diagnostic assays has improved since 2020, when our group first demonstrated that most HHM diagnostic tests were insufficient for the accurate diagnosis of these syndromes. We hypothesized that the number of genes tested on each HHM assay increased from 2020 to 2022, in keeping with a more comprehensive sequencing approach.

Design, Setting, and Participants

We analyzed assays from eight commercial laboratories to determine which HHM-related genes were sequenced by these assays. We compared these assays to panels from 2020 to determine trends in sequencing quality.

Results

The majority of HHM diagnostic assays did not change over time and are insensitive for the detection of the full spectrum of HHM-related mutations. The majority (75%) of HHM assays do not sequence CHEK2, the gene most frequently mutated in HHMs, and 25% of HHM assays do not sequence DDX41, the second most frequently mutated HHM gene.

Conclusions

The quality of HHM diagnostic assays has stagnated despite the discovery of novel HHM-related genes as well as prior work demonstrating heterogeneity in quality of HHM testing. The majority of commercially available HHM tests remain insufficient for the diagnosis of the full spectrum of HHM-related germline mutations.

Key Points

Question

How have diagnostic assays for hereditary hematopoietic malignancies (HHMs) changed since 2020, when most HHM diagnostic assays were inadequate for the accurate diagnosis of HHMs?

Findings

Most HHM assays have significant deficiencies in quality and do not sequence the most relevant HHM-related genes. No meaningful improvements in the quality of HHM diagnostic testing have occurred since 2020.

Meaning

The quality of HHM diagnostic testing must be improved to universally include the most common HHM-related germline mutations. This will reduce the risk for false negatives, donor derived leukemias, improve genetic counseling, and improve screening for other HHM-related malignancies.
Use of systemic hormonal contraception and risk of attempted suicide
Authors: Toffol Elena , Heikinheimo Oskari , Partonen Timo , But Anna , Latvala Antti , Haukka Jari
Published: June 2022

Background

Evidence regarding the role of hormonal contraception (HC) as a risk factor for attempted suicide (AS) is inconclusive. The aim was to assess the associations of use of different types of systemic hormonal contraceptives with the risk of AS in women aged 15–49 years.

Methods

Data were retrieved from national registers in Finland. The AS incidence in 2018-2019 was assessed in a population-based cohort of women (n=587,823) according to their HC use in 2017. To examine the risk of AS related to HC use in the six months preceding the suicide attempt (i.e. current use), we used a nested case-control design with 1:4 ratio (n=4090), and applied multivariable conditional logistic regression models.

Results

During the follow-up 1.174,346 million person-years were cumulated and 818 AS cases observed (incidence rate=0.70, 95% CI=0.63–0.83 per 1000 person-years). The incidence rate ratio of HC (n=344 cases) vs. no-HC (n=474 cases) was 0.73 (95% CI=0.63–0.83). Use of HC, and specifically of combined hormonal contraceptives was associated with a lower AS risk compared to non-use when controlling for marital status, socioeconomic status, education, chronic diseases and recent delivery (OR=0.55, 95% CI=0.42–0.73), but not when further adjusting for recent psychiatric hospitalizations and current use of psychotropic medications (OR=0.68, 95% CI=0.45–1.02). Current use of progestogen-only preparations was not associated with AS.

Conclusions

HC use appeared not associated with an increased AS risk in fertile-aged women. The choice of the best and safest contraceptive option should take individual mental health status, including assessment of suicidal risk, into account.