bluuebunny/crossref_metadata_2025 huggingface dataset:
Ethical implications of AI and robotics in healthcare: A review
Authors: Elendu Chukwuka , Amaechi Dependable C. , Elendu Tochi C. , Jingwa Klein A. , Okoye Osinachi K. , John Okah Minichimso , Ladele John A. , Farah Abdirahman H. , Alimi Hameed A.
Published: December 2023

Integrating Artificial Intelligence (AI) and robotics in healthcare heralds a new era of medical innovation, promising enhanced diagnostics, streamlined processes, and improved patient care. However, this technological revolution is accompanied by intricate ethical implications that demand meticulous consideration. This article navigates the complex ethical terrain surrounding AI and robotics in healthcare, delving into specific dimensions and providing strategies and best practices for ethical navigation. Privacy and data security are paramount concerns, necessitating robust encryption and anonymization techniques to safeguard patient data. Responsible data handling practices, including decentralized data sharing, are critical to preserve patient privacy. Algorithmic bias poses a significant challenge, demanding diverse datasets and ongoing monitoring to ensure fairness. Transparency and explainability in AI decision-making processes enhance trust and accountability. Clear responsibility frameworks are essential to address the accountability of manufacturers, healthcare institutions, and professionals. Ethical guidelines, regularly updated and accessible to all stakeholders, guide decision-making in this dynamic landscape. Moreover, the societal implications of AI and robotics extend to accessibility, equity, and societal trust. Strategies to bridge the digital divide and ensure equitable access must be prioritized. Global collaboration is pivotal in developing adaptable regulations and addressing legal challenges like liability and intellectual property. Ethics must remain at the forefront in the ever-evolving realm of healthcare technology. By embracing these strategies and best practices, healthcare systems and professionals can harness the potential of AI and robotics, ensuring responsible and ethical integration that benefits patients while upholding the highest ethical standards.
Identification of central genes for endometriosis through integration of single-cell RNA sequencing and bulk RNA sequencing analysis
Authors: Song Yulin , Wang Le , Zhang Yu
Published: December 2023

This study aimed to identify the key genes involved in the development of endometriosis and construct an accurate predictive model to provide new directions for the diagnosis and treatment of endometriosis. Using bioinformatics analysis, we employed the single-cell cell communication method to identify the key cell subtypes. By combining chip data and integrating differential analysis, WGCNA analysis, and the least absolute shrinkage and selection operator (LASSO) model, key genes were identified for immune infiltration and functional enrichment analyses. Cell communication analysis identified tissue stem cells as the key subtype. Differential analysis revealed 1879 differentially expressed genes, whereas WGCNA identified 357 module genes. The LASSO model further selects 4 key genes: Adipocyte Enhancer Binding Protein 1(AEBP1), MBNL1, GREM1, and DES. All 4 key genes showed significant correlations with immune cell content. Moreover, these genes were significantly expressed in single cells. The predictive model demonstrated good diagnostic performance. Through scRNA-seq, WGCNA, and LASSO methodologies, DES, GREM1, MBNL1, and AEBP1 emerged as crucial core genes linked to tissue stem cell markers in endometriosis. These genes have promising applications as diagnostic markers and therapeutic targets for endometriosis.
Impact of the COVID-19 pandemic on the operations of the specialty hospital department in Beijing
Authors: Wang Mengqin , Tian Zhaoxing
Published: December 2023

The coronavirus disease 2019 (COVID-19) pandemic was disruptive to non-COVID-19-related healthcare. This study aimed to compare patient inflows and patient population characteristics at the Hand Surgery Department of JiShuiTan (JST) Hospital in Beijing, a top referral center, in 2020 during the pandemic relative to the same period in 2019. This cross-sectional study was conducted to analyze the impact of the COVID-19 pandemic on patients admitted to the hand surgery ward. The participants were patients admitted from January to April 2019 (J–A19) and from January to April 2020 (J–A20). The medical records were analyzed, including age, sex, admission time, admission mode, admission diagnosis, and patient residence. Significantly fewer patients were admitted in J–A20 than in J–A19, with particularly dramatic reductions observed for non-Beijing residents and nonemergency cases (e.g., congenital anomalies operations for children). The top 5 diagnosis types for admitted patients were consistent throughout J–A19 and in January 2020. The rank of the diagnostic type “open injuries of the hand and wrist” increased significantly in February, March, and April of 2020 compared with 2019. The COVID-19 pandemic decreased patient admissions, especially for nonemergency patients, during J–A20.
Effect of medical choice and health behavior on the health status for patients with subluxation of the sacroiliac joint
Authors: Zhang Wenhui , Wang Xingxin , Liu Yuanxiang , Yang Jiguo
Published: December 2023

The sacroiliac joint is an important part of human life behavior and daily activities. With the increase in people’s lives and work pressure and the change of travel mode, the incidence rate of sacroiliac joint subluxation is getting higher and higher. The purpose of this study is to explore the relationship between medical choice, health behavior, and health status of patients with sacroiliac joint subluxation and put forward feasible suggestions for promoting the treatment and rehabilitation of patients. The EuroQoL 5 Dimensions 5 Levels health index survey scale was selected to investigate the health status of patients with sacroiliac joint subluxation. T test and analysis of variance were used for univariate analysis of medical choice and health behavior of patients with sacroiliac subluxation, and ordinary least squares was used for multivariate analysis. The elderly patients with subluxation of sacroiliac joint are in poor health. The health status of patients who chose to seek medical treatment for disease diagnosis and prescription was significantly worse. Patients with subluxation of sacroiliac joint with regular defecation have better health status. Patients who travel by bike or bus have worse health. The health status of those who sit still for more than 1 hour a day is significantly better. The health status of patients with sacroiliac subluxation is closely related to their choice of medical treatment and health behavior. It is suggested that rehabilitation therapy such as acupuncture and manipulation should be selected for intervention. Good health behaviors such as abstinence and regular defecation should be shaped. More attention should be paid to the health status of women at risk.
A systematic review and meta-analysis of moxibustion for chronic prostatitis
Authors: Yu Xi-wen , Wang Cheng-si , Yu Xiao-hong
Published: December 2023

Background:

Chronic prostatitis (CP) is a common condition that affects many individuals. Previous clinical trials have explored the use of moxibustion as a potential treatment for CP. However, the evidence on the effectiveness of moxibustion for CP remains limited. Therefore, this study aimed to comprehensively assess the effects of moxibustion for CP.

Methods:

In order to gather relevant and up-to-date information, we conducted a systematic literature search of databases including Cochrane Library, PUBMED, EMBASE, CNKI, and Wangfang from inception until June 30, 2023. Only randomized clinical trials (RCTs) that investigated the use of moxibustion for CP were included in this study. The primary outcomes of interest were the National Institutes of Health-Chronic Prostatitis Symptom Index (NIH-CPSI) scores and the overall response rate. To evaluate the quality of the included studies, we used the Cochrane risk-of-bias tool.

Results:

After analyzing the data from 8 RCTs involving a total of 664 patients, we found significant differences in NIH-CPSI scores between moxibustion and other treatment modalities. Specifically, when compared with herbal medicine, moxibustion was associated with a mean difference (MD) of −1.78 in NIH-CPSI scores (95% confidence interval [CI] [−2.78, −0.78], P < .001), and when compared with western medicine, moxibustion was associated with a MD of −5.24 in NIH-CPSI scores (95% CI [−7.80, −2.67], P < .08). In terms of the overall response rate, moxibustion was found to be superior to herbal medicine, with a MD of 2.36 (95% [19, 4.67], P = .01). Additionally, when moxibustion was combined with herbal medicine, it yielded a higher overall response rate with a MD of 4.07 (95% CI [1.54, 10.74], P = .005) compared to herbal medicine alone. Moxibustion also outperformed western medicine in terms of the overall response rate, with a MD of 4.56 (95% CI [2.24, 9.26], P < .001).

Conclusion:

Based on the findings of this study, moxibustion appears to be a potentially efficacious treatment for CP. The results suggest that moxibustion can improve NIH-CPSI scores and overall response rate in patients with CP. However, further high-quality studies are needed to validate these results and establish the long-term effects of moxibustion as a treatment for CP.
Central Sensitization in Vulvodynia and Endometriosis: What Have We Been Overlooking So Far?
Authors: Cetera Giulia Emily , Merli Camilla Erminia Maria , Boero Veronica , Caia Carlotta , Facchin Federica , Barbara Giussy , Monti Ermelinda , Vercellini Paolo
Published: December 2023

Importance

Women experience more frequent and greater pain than men, although they receive less adequate treatment and are perceived as more anxious than males. Recent clinical research has lead to hypothesize a common etiology for overlapping chronic pain conditions and mood disorders, namely, central sensitization, which originates from an alteration of pain processing pathways in the central nervous system.

Objective

The aim of this review was to collect all available evidence regarding the potential role of central sensitization in vulvodynia and endometriosis.

Evidence Acquisition

A systematic literature search was performed between July and August 2022 using the electronic database PubMed. The extracted data were summarized using a narrative approach.

Results

Ten articles were chosen for the review. Participants' mean age was 39.2 years (SD = 5.1). Among serum markers of central sensitization, nitric oxide levels were greater in women with endometriosis than in controls, whereas brain-derived neurotrophic factor and S100B levels differed among pain conditions with structural anomalies and those without. Functional magnetic resonance imaging showed different resting state networks between patients with endometriosis and controls. In neurophysiology studies, cases had reduced pain thresholds, compared with healthy controls. Lastly, self-reported questionnaires suggested a central component of pain in women with endometriosis-related dyspareunia and associated bladder/pelvic floor tenderness.

Conclusions and Relevance

The management of vulvodynia and endometriosis may benefit from a new perspective, which considers their possible central etiology. It is compelling that treatment of pain starts to be considered a therapeutic goal in its own right.

Target Audience

Obstetricians and gynecologists, family physicians.

Learning Objectives

After completing this activity, the learner should be better able to describe central sensitization as a common etiology for vulvodynia and endometriosis; explain how to investigate the presence of central sensitization with various techniques; identify the possible origin of vulvodynia and endometriosis pain; and discuss the importance of considering treatment of pain as a therapeutic goal.
Spontaneous Rupture of the Unscarred Uterus: A Review of the Literature
Authors: Sgayer Inshirah , Dabbah Shirin , Farah Rola Khamisy , Wolf Maya , Ashkar Nadine , Lowenstein Lior , Odeh Marwan
Published: December 2023

Importance

Uterine rupture is defined as a nonsurgical disruption of all layers of the uterus. Most ruptures occur in the presence of a scar, usually secondary to a previous cesarean delivery. Rupture of an unscarred uterus is rare and is associated with severe maternal and neonatal outcomes.

Objective

To outline the literature on potential predisposing factors, clinical findings, and maternal and fetal outcomes of a rupture of an unscarred uterus.

Evidence Acquisition

PubMed was searched for the phrases “uterine rupture,” “unscarred,” and “spontaneous.” Individual case reports, retrospective case series, and review articles in English between 1983 and 2020 were included.

Results

We found 84 case reports in 79 articles. The mean maternal age was 29.3 (SD, 5.7) years; 38 women (45.2%) were nulliparous. Uterine rupture occurred in 37% of the women at term; in 9.9%, the gestational age was ≤12 weeks. The most common clinical presentations were abdominal pain (77.4%), signs of hypovolemic shock (36.9%), fetal distress (31%), and vaginal bleeding (22.6%). The most common risk factors were the use of uterotonic drugs for induction or augmentation of labor and a prior curettage procedure. The most frequently ruptured site was the body of the uterus. Hysterectomy managed 36.9% of the ruptures. Four women died (4.8%). Perinatal mortality was 50.6%. Perinatal death was higher in developing than developed countries.

Conclusions and relevance

Although rare, spontaneous rupture of the unscarred uterus has serious consequences to the mother and the fetus and should be included in the differential diagnosis of acute abdomen in pregnancy.

Target Audience

Obstetrician-gynecologists, family medicine physicians.

Learning Objectives

After completing this activity, the learner will be better able to describe the consequences of spontaneous rupture of the unscarred uterus to the mother and fetus; discuss risk factors for spontaneous rupture of the unscarred uterus and its potential occurrence in nulliparous, antepartum, and the first trimester; and discuss how timely assessment of a pregnant woman presenting with abdominal pain impacts survival of the mother and child.
Prevention of Early-Onset Neonatal Group B Streptococcal Disease: A Comprehensive Review of Major Guidelines
Authors: Boureka Eirini , Krasias Dimitrios , Tsakiridis Ioannis , Karathanasi Anna-Maria , Mamopoulos Apostolos , Athanasiadis Apostolos , Dagklis Themistoklis
Published: December 2023

Importance

Group B Streptococcus (GBS) colonization during pregnancy is associated with significant neonatal morbidity and mortality and represents a major public health concern, often associated with poor screening and management.

Objective

The aim of this study was to review and compare the most recently published influential guidelines on the screening and management of this clinical entity during antenatal and intrapartum periods.

Evidence Acquisition

A descriptive review of guidelines from the American College of Obstetricians and Gynecologists, the Royal College of Obstetricians and Gynecologists, the Royal Australian and New Zealand College of Obstetricians and Gynecologists, and the Society of Obstetricians and Gynecologists of Canada on the prevention of early-onset neonatal group B streptococcal disease was carried out.

Results

There is a consensus among the reviewed guidelines regarding the optimal screening specimen type, indications for intrapartum antibiotic administration such as bacteriuria during pregnancy, clinical signs of chorioamnionitis or maternal pyrexia, and history of GBS-related neonatal disease. There is also agreement on several conditions where no intervention is recommended, that is, antepartum treatment of GBS and GBS-positive women with planned cesarean delivery and intact membranes. Controversy exists regarding the optimal screening time, with the Royal College of Obstetricians and Gynecologists stating against routine screening and on management strategies related to preterm labor and preterm prelabor rupture of membranes.

Conclusions

The development of consistent international practice protocols for the timely screening of GBS and effective management of this clinical entity both during pregnancy and the intrapartum period seems of paramount importance to safely guide clinical practice and subsequently improve neonatal outcomes.

Target Audience

Obstetricians and gynecologists, family physicians

Learning Objectives

After participating in this activity, the learner should be better able to explain the aim of screening for group B streptococcal infection in pregnancy; identify cases that should be treated for group B streptococcal infection; and discuss appropriate intrapartum antibiotic prophylaxis for pregnant women positive for GBS.
Safety of Vaginal Estrogen Therapy for Genitourinary Syndrome of Menopause in Women With a History of Breast Cancer
Authors: Agrawal Pranjal , Singh Sajya M. , Able Corey , Dumas Kathryn , Kohn Jaden , Kohn Taylor P. , Clifton Marisa
Published: December 2023

(Abstracted from Obstet Gynecol 2023;142:660–668)

The current 5-year survival rate for female breast cancer patients has risen to 90%, but several breast cancer systemic treatments such as radiotherapy, chemotherapy, and endocrine therapy can all worsen hypoestrogenic states. Genitourinary syndrome of menopause (GSM) can result from lack of circulating estrogen, which can possibly lead to conditions such as sexual dysfunction.
Surgical management and weight-bearing recommendations for geriatric distal femur fractures
Authors: Haller Justin M. , Marchand Lucas S. , Higgins Thomas F. , O'Toole Robert V. , Reider Lisa
Published: December 2023

Objective:

To investigate current practices among orthopaedic trauma surgeons in treating geriatric distal femur fractures and evaluate current postoperative weight-bearing recommendations.

Methods:

A 26-question survey was emailed to Major Extremity Trauma Research Consortium surgeon members to characterize current practice with different fixation methods for distal femur fractures and the surgeon-directed postoperative weight-bearing recommendations for each approach.

Results:

Surveys were completed by 123 orthopaedic trauma surgeons with a response rate of 37% (123/332). Retrograde intramedullary nailing (IMN) was commonly performed by 88% of surgeons, and lateral locked plate was commonly performed by 74% of surgeons. Retrograde IMN with a lateral plate was commonly performed by 51% of surgeons. Dual femoral plating was commonly performed by 18% of surgeons and sometimes performed by 39% of surgeons. Surgeons were significantly more likely to allow immediate postoperative weight-bearing for retrograde IMN (P< 0.001), retrograde IMN with lateral plate (P< 0.001), and dual plate (P< 0.001) as compared with locked lateral plate. Most surgeons (79%) would be interested in participating in a randomized controlled trial (RCT) investigating single implant versus dual implant for distal femur fractures and believe that a trial incorporating immediate weight-bearing is important.

Conclusion:

A variety of implants are commonly used to treat geriatric distal femur fractures. Patients with distal femur fracture commonly have weight-bearing restrictions in the immediate postoperative period. A large proportion of orthopaedic trauma surgeons have clinical equipoise for an RCT to investigate the impact of surgical construct and weight-bearing on geriatric distal femur fracture patient recovery.
Examination of Incidence of Sexually Transmitted Infections in the Ending the HIV Epidemic Priority Counties of the U.S., 2005-2019
Authors: Bunting Samuel R. , Hunt Bijou , Johnson Amy K. , Hazra Aniruddha , Nunez-Garcia Andrea , Glick Nancy
Published: December 2023

Background

The incidence of sexually transmitted infections (STIs) has been increasing in the U.S. and this trend has continued alongside expanding/changing HIV-prevention strategies, moving from reliance solely on behavioral interventions like condoms to biomedical methods like oral and injectable antiretroviral pre-exposure prophylaxis (PrEP). In 2019, the Ending the HIV Epidemic (EHE) initiative was released to prioritize resource allocation to the 50 jurisdictions in the U.S. with the highest HIV incidence, providing an opportunity to monitor STI incidence in a national group of discrete, geographic units and identify trends and differences across jurisdictions.

Objectives & Design

Using existing data from the U.S. CDC and Census Bureau, a retrospective analysis was conducted to examine the incidence of STIs in 49 of the 50 EHE priority counties between 2005-2019. This timeframe was divided into two time periods representing a before and after entry into the biomedical era of HIV-prevention: P1 (2005-2011) and P2 (2012-2019).

Key Results

A total of 49 EHE counties were included in this analysis, representing 27.4% of the total U.S. population. Entry into the biomedical HIV-prevention era was associated with an increase in STI incidence in 28 EHE counties and a decrease in 14 EHE counties. The greatest percent increase in total STI incidence was in the District of Columbia (+12.1%; IRR = 1.121, [1.115, 1.127], p < .001) and the greatest percent decrease was identified in Orleans Parish, LA (-8.7%; IRR = 0.913, [0.908, 0.919], p < .001).

Conclusions

Rising STI rates in the biomedical era of HIV-prevention represent missed opportunities for comprehensive sexual and preventive healthcare. County-level data provide actionable insight for reducing STI incidence. The EHE counties that have experienced decreases in STI incidence while being in the biomedical era may provide models of best practice which may be scaled in other jurisdictions.
Admission Functional Status is Associated With Intensivists Perception of Extracorporeal Membrane Oxygenation Candidacy for Pediatric Acute Respiratory Failure
Authors: McCabe Brenna C. , Morrison Wynne E. , Morgan Ryan W. , Himebauch Adam S.
Published: December 2023

OBJECTIVES:

To determine the association between admission Functional Status Scale (FSS) category and perceived extracorporeal membrane oxygenation (ECMO) candidacy for pediatric acute respiratory failure.

DESIGN:

Prospective, cross-sectional study.

SETTING:

Single-center, quaternary, and ECMO referral academic children’s hospital between March 2021 and January 2022.

SUBJECTS:

Pediatric intensivists directly caring for patients admitted with acute respiratory failure secondary to shock or respiratory disease.

INTERVENTIONS:

None.

MEASUREMENTS AND MAIN RESULTS:

Pediatric intensivists were surveyed about current patients within 72 hours of initiation or escalation of invasive mechanical ventilation on whether they would offer ECMO should their patient deteriorate. Baseline functional status was assessed using trichotomized admission FSS: 1) normal/mild dysfunction (6–9), 2) moderate dysfunction (10–15), and 3) severe dysfunction (> 16). Multivariable logistic regression clustered by physician was used to assess the association between admission FSS category with perceived ECMO candidacy. Thirty-seven intensivists participated with 76% (137/180) of survey responses by those with less than 10 years of experience. 81% of patients (146/180) were perceived as ECMO candidates and 19% of patients (34/180) were noncandidates. Noncandidates had worse admission FSS scores than candidates (15.5 vs. 9, p < 0.001). After adjustment for age, admission FSS category of severe dysfunction had lower odds of perceived ECMO candidacy compared with normal to mild dysfunction (odds ratio [OR] 0.18 [95% CI, 0.06–0.56], p < 0.003). Patients with an abnormal communication subscore domain had the lowest odds of being considered a candidate (unadjusted OR 0.44 [95% CI, 0.29–0.68], p < 0.0001).

CONCLUSIONS:

In this prospective, single-center, cross-sectional study, admission FSS category indicating worse baseline functional status impacted pediatric intensivists’ perceptions of ECMO candidacy for patients with acute respiratory failure. Abnormal FSS subscores in the neurocognitive domains were the most important considerations. Future studies should better seek to define the decision-making priorities of both parents and medical specialists for the utilization of ECMO in children with acute respiratory failure.
An improved genome editing system for Sphingomonadaceae
Authors: García-Romero Inmaculada , de Dios Rubén , Reyes-Ramírez Francisca
Published: December 2023

The sphingomonads encompass a diverse group of bacteria within the Sphingomonadaceae family, with the presence of sphingolipids on their cell surface instead of lipopolysaccharide as their main common feature. They are particularly interesting for bioremediation purposes due to their capability to degrade or metabolise a variety of recalcitrant organic pollutants. However, the research and development of their full bioremediation potential has been hampered because of the limited number of tools available to investigate and modify their genome. Here, we present a markerless genome editing method for Sphingopyxis granuli, which can be further optimised for other sphingomonads. This procedure is based on a double recombination triggered by a DNA double strand break in the chromosome. The strength of this protocol lies in forcing the second recombination rather than favouring it by pressing a counterselection marker, thus avoiding laborious re-streaking or passaging screenings. Additionally, we introduce a modification with respect to the original protocol to increase the efficiency of the screening after the first recombination event. We show this procedure step by step and compare our modified method with respect to the original one by deleting ecfG2, the master regulator of the general stress response in S. granuli. This adds onto the genetic tool repertoire that can be applied to sphingomonads and stands as an efficient option for fast genome editing of this bacterial group.
Discordance between different bioinformatic methods for identifying resistance genes from short-read genomic data, with a focus on Escherichia coli
Authors: Davies Timothy J. , Swann Jeremy , Sheppard Anna E. , Pickford Hayleigh , Lipworth Samuel , AbuOun Manal , Ellington Matthew J. , Fowler Philip W. , Hopkins Susan , Hopkins Katie L. , Crook Derrick W. , Peto Timothy E. A. , Anjum Muna F. , Walker A. Sarah , Stoesser Nicole
Published: December 2023

Several bioinformatics genotyping algorithms are now commonly used to characterize antimicrobial resistance (AMR) gene profiles in whole-genome sequencing (WGS) data, with a view to understanding AMR epidemiology and developing resistance prediction workflows using WGS in clinical settings. Accurately evaluating AMR in Enterobacterales, particularly

Escherichia coli

, is of major importance, because this is a common pathogen. However, robust comparisons of different genotyping approaches on relevant simulated and large real-life WGS datasets are lacking. Here, we used both simulated datasets and a large set of real

E. coli

WGS data (n=1818 isolates) to systematically investigate genotyping methods in greater detail. Simulated constructs and real sequences were processed using four different bioinformatic programs (ABRicate, ARIBA, KmerResistance and SRST2, run with the ResFinder database) and their outputs compared. For simulation tests where 3079 AMR gene variants were inserted into random sequence constructs, KmerResistance was correct for 3076 (99.9 %) simulations, ABRicate for 3054 (99.2 %), ARIBA for 2783 (90.4 %) and SRST2 for 2108 (68.5 %). For simulation tests where two closely related gene variants were inserted into random sequence constructs, KmerResistance identified the correct alleles in 35 338/46 318 (76.3 %) simulations, ABRicate identified them in 11 842/46 318 (25.6 %) simulations, ARIBA identified them in 1679/46 318 (3.6 %) simulations and SRST2 identified them in 2000/46 318 (4.3 %) simulations. In real data, across all methods, 1392/1818 (76 %) isolates had discrepant allele calls for at least 1 gene. In addition to highlighting areas for improvement in challenging scenarios, (e.g. identification of AMR genes at <10× coverage, identifying multiple closely related AMR genes present in the same sample), our evaluations identified some more systematic errors that could be readily soluble, such as repeated misclassification (i.e. naming) of genes as shorter variants of the same gene present within the reference resistance gene database. Such naming errors accounted for at least 2530/4321 (59 %) of the discrepancies seen in real data. Moreover, many of the remaining discrepancies were likely ‘artefactual’, with reporting of cut-off differences accounting for at least 1430/4321 (33 %) discrepants. Whilst we found that comparing outputs generated by running multiple algorithms on the same dataset could identify and resolve these algorithmic artefacts, the results of our evaluations emphasize the need for developing new and more robust genotyping algorithms to further improve accuracy and performance.
Lifestyle differences between co-twins are associated with decreased similarity in their internal and external exposome profiles
Authors: Drouard Gabin , Wang Zhiyang , Heikkinen Aino , Foraster Maria , Julvez Jordi , Kanninen Katja M. , van Kamp Irene , Pirinen Matti , Ollikainen Miina , Kaprio Jaakko
Published: December 2023

Whether differences in lifestyle between co-twins are reflected in differences in their internal or external exposome profiles remains largely underexplored. We therefore investigated whether within-pair differences in lifestyle were associated with within-pair differences in exposome profiles across four domains: the external exposome, proteome, metabolome and epigenetic age acceleration (EAA). For each domain, we assessed the similarity of co-twin profiles using Gaussian similarities in up to 257 young adult same-sex twin pairs (54% monozygotic). We additionally tested whether similarity in one domain translated into greater similarity in another. Results suggest that a lower degree of similarity in co-twins’ exposome profiles was associated with greater differences in their behavior and substance use. The strongest association was identified between excessive drinking behavior and the external exposome. Overall, our study demonstrates how social behavior and especially substance use are connected to the internal and external exposomes, while controlling for familial confounders.
Securin Regulates the Spatiotemporal Dynamics of Separase
Authors: Turpin Christopher G. Sorensen , Sloan Dillon , LaForest Marian , Klebanow Lindsey Uehlein , Mitchell Diana , Severson Aaron F. , Bembenek Joshua N.
Published: December 2023

Separase is a key regulator of the metaphase to anaphase transition with multiple functions. Separase cleaves cohesin to allow chromosome segregation and localizes to vesicles to promote exocytosis in mid-anaphase. The anaphase promoting complex/cyclosome (APC/C) activates separase by ubiquitinating its inhibitory chaperone, securin, triggering its degradation. How this pathway controls the exocytic function of separase has not been investigated. During meiosis I, securin is degraded over several minutes, while separase rapidly relocalizes from kinetochore structures at the spindle and cortex to sites of action on chromosomes and vesicles at anaphase onset. The loss of cohesin coincides with the relocalization of separase to the chromosome midbivalent at anaphase onset. APC/C depletion prevents separase relocalization, while securin depletion causes precocious separase relocalization. Expression of non-degradable securin inhibits chromosome segregation, exocytosis, and separase localization to vesicles but not to the anaphase spindle. We conclude that APC/C mediated securin degradation controls separase localization. This spatiotemporal regulation will impact the effective local concentration of separase for more precise targeting of substrates in anaphase.
A multiplex qRT-PCR assay for detection of Influenza A and H5 subtype targeting new SNPs present in high pathogenicity avian influenza Canadian 2022 outbreak strains
Authors: Lee Tracy D. , Tsang Frankie , Kolehmainen Kathleen , Prystajecky Natalie A. , Jassem Agatha N. , Tyson John R.
Published: December 2023

H5N1 is a highly pathogenic avian Influenza A subtype that has been known to also infect mammalian hosts and presents a potential public health risk. To address and mitigate the affects of new SNPs, found in recent Canadian outbreaks, on diagnostic detection we developed two qRT-PCR assays by modifying current probes to match sequences detected in the east and west coast of Canada. These assays were multiplexed with a third qRT-PCR assay targeting the M segment, allowing streamlined detection of Influenza A and subtyping for H5. This three-plex qRT-PCR was validated by assessing analytical specificity, limit-of-detection, precision, and accuracy.
Associations between early-life mental health and abnormal sleep duration in midlife: findings from a prospective cohort study in Great Britain
Authors: Metherell Thomas E. , Ploubidis George B. , Moreno-Agostino Darío
Published: December 2023

Objectives

To quantify the association between the state of mental health in childhood and sleep duration at age 46-48 in the 1970 British Cohort Study (BCS70).

Design

BCS70 is a prospective birth cohort study of a population-representative sample.

Setting

Data collection was conducted in participants’ homes across Great Britain.

Participants

All individuals born in one week in April 1970 and resident in the UK are eligible to take part, including those born outside the UK who subsequently immigrated. The study has more than 17,000 participants, of whom 8,581 responded at the last available sweep at age 46-48.

Main outcome measures

Average nightly sleep duration at age 46-48, as assessed by five separate methods: self-report, inference from a sleep diary and three algorithms used to process accelerometry data collected using a thigh-worn activPAL™ 3 device.

Results

All seven measures of childhood mental ill-health were positively associated with abnormal self-reported sleep duration. Five were associated with abnormal diary-derived estimates and four were associated with abnormal estimates from an accelerometry-based algorithm. Strengths of associations vary. Adjusting for adult mental health symptoms partially attenuated the associations with self-reported sleep duration but not with the more objective estimates.

Conclusions

Poor mental health in childhood is associated with abnormal nightly sleep duration at age 46-48. Post-hoc analyses suggest that this association might not be entirely mediated by poor mental health in adulthood. Future research should attempt to replicate these results in diverse samples and assess whether stronger interventions in early-life mental health might have substantial and long-lasting positive impacts on sleep.

What is already known on this topic

The state of a person’s mental health in their early life is associated with a range of adult health outcomes.

There exists a bidirectional and multifaceted relationship between the state of a person’s mental health and their sleep.

The longitudinal association between early-life mental health and sleep in adulthood was not well understood.

What this study adds

Our study demonstrates that early-life mental health is associated with an abnormal average nightly sleep duration at age 46 in this sample.

Associations between early-life mental health and abnormal average nightly sleep at age 46 were not fully mediated by adult mental health.
Socioeconomic inequities in care experienced by women with breast cancer in England: An intersectional cross-sectional study
Authors: de Mesa Mar Estupiñán Fdez , Marcu Afrodita , Ream Emma , Whitaker Katriina L
Published: December 2023

Purpose

Guided by the intersectionality framework, we examined the differential in breast cancer care experience across population subgroups in England.

Methods

Secondary data analysis using the 2017/2018 English National Cancer Patient Experience Survey (NCPES). We applied disaggregated descriptive statistics (mean, standard errors, 95% confidence interval) to analyse 26,030 responses from female breast cancer patients to a question relating to overall care experience categorised by age, ethnicity, and sexual orientation in their intersection with deprivation status. We then applied multivariable logistic regression (odds ratios, 95% confidence intervals) to ascertain the relationship of reporting a positive care experience adjusting for patient, clinical, and trust-level factors.

Results

Poorer breast cancer care experience was mostly reported by the most deprived younger and minoritised ethnic groups. Similar findings were observed in adjusted multivariable analyses. Younger respondents were less likely than older patients to rate their care favourably. Pakistani, Indian, Chinese, and Black African women were less likely than White British women to rate their care favourably. Respondents from the most socioeconomic deprived backgrounds were less likely than the most affluent ones to rate their care favourably.

Conclusion

There is evidence of inequity in overall cancer care experience among female breast cancer patients in England, particularly among women living at the specific intersection of age, ethnicity and socioeconomic position. Future research is necessary to understand the mechanisms underlying breast cancer inequities. Policymakers, commissioners, and providers should consider the existence of multiple forms of marginalization to inform improvement initiatives targeting patients at higher risk of vulnerability.
Physiotherapists’ use of aerobic exercise during stroke rehabilitation: a qualitative study using chart-stimulated recall
Authors: Barzideh Azadeh , Devasahayam Augustine Joshua , Tang Ada , Inness Elizabeth , Marzolini Susan , Munce Sarah , Sibley Kathryn M , Mansfield Avril
Published: December 2023

Purpose

We aimed to explore the factors that affect physiotherapists’ use of AE during stroke rehabilitation for people with stroke.

Material and methods

We conducted a qualitative descriptive study using thematic analysis informed by a pragmatic worldview. Physiotherapists attended one on one semi-structured interviews to answer some general questions about aerobic exercise and then discussed the charts of their 4 most recently discharged patients. Both deductive and inductive coding were used for analysis.

Results

Ten physiotherapists participated. Healthcare policies and limited resources were mostly discussed in general questions while specific profiles of patients with stroke, their goals and preferences were mostly discussed in patient specific questions. Three themes were identified:1) physiotherapists’ perspectives and practices around aerobic exercise; 2) profiles of people with stroke, as well as their goals and their exercise modality preferences; and 3) influence of health system priorities, rehabilitation intensity policy, and resources.

Conclusions

Physiotherapists’ behaviours regarding use of aerobic exercise for people with stroke are not a binary behaviour of prescribing or not prescribing aerobic exercise. Their behaviours are better understood on a continuum; between two ends of not prescribing aerobic exercise, and prescribing aerobic exercise with defined intensity, duration, and frequency.
Types and timing of trauma exposure across the life course and maternal hypertension
Authors: Stanhope Kaitlyn K , Michopoulos Vasiliki , Powers Abigail , Boulet Sheree L , Kramer Michael R , Suglia Shakira F
Published: December 2023

Objective

To estimate associations between types and timing (first occurrence and time since) of trauma exposure and hypertension experienced during pregnancy in a safety-net hospital in Atlanta, Georgia.

Methods

Participants completed a 14-item trauma screener. We linked that information to data from the medical record on hypertension (inclusive of chronic hypertension, gestational hypertension, or preeclampsia). We fit logistic regression models and used the estimates to calculate risk ratios for each trauma type and each critical window (0-9 years, 10-19, and 20+). We fit unadjusted models and adjusted for age, parity, and education.

Results

We included 704 individuals with a delivery within 12 months of screening. The majority (94%, 661) reported at least one traumatic event, most commonly witnessing violence (79.4%). Overall, 18% experienced gestational hypertension, 10.8% chronic hypertension, and 11.9% preeclampsia. Among individuals who reported trauma, 31.5% screened positive for probable posttraumatic stress disorder and 30.9% for probable depression compared to 0 and 2.3% among those without reported trauma. No trauma type (violence, witnessing violence, non-interpersonal, or sexual assault) was associated with increased hypertensive risk, regardless of timing. Similarly, time between trauma and delivery (0-3 years, 3-10 years, 10+ years) was not associated with increased hypertensive risk.

Conclusions

In this sample with a high trauma and hypertension burden, trauma was not associated with elevated risk of hypertension during pregnancy, despite a high burden of PTSD and depressive symptoms among people with trauma exposure. Future research should consider how community-level exposure may modify the impact of trauma on adverse pregnancy outcomes.
Integrated bioinformatics and wet-lab analysis revealed prominent inflammatory genes of Extracellular Matrix as prognostic biomarkers in patients with advance IBD requiring early surgery
Authors: Dehghani Mahmoudabadi Farzad , Khanabadi Binazir
Published: December 2023

Background

The number of patients with inflammatory bowel disease (IBD) is increasing worldwide. Due to the fact that at the age of 20 to 30 years, this autoimmune disease is very common; Investigating and identifying prognostic biomarkers in advanced IBD is very important; Because according to the identification of these biomarkers, patients who need early surgery can be nominated and undergo surgery without wasting time and treatment costs. In this study, with the aim of identifying effective biomarkers involved in the inflammatory part of extracellular matrix (ECM) in the early surgery of IBD, separately from Crohns disease and ulcerative colitis.

Method

In this study, we examined 50 patients in both patient groups as well as the normal group. The expression of the nominated genes MASP2, DKC1, HNF4A, and STAT3 was analyzed using quantitative polymerase chain reaction (Q-PCR) and relative quantification was determined using the 2-ΔΔCtmethod. ROC curve analysis was performed to compare IBD (UC & CD) and normal for the investigated genes. The correlation between adhesion molecule gene expression and immunophenotype was analyzed. Also we comprehensively analyzed the genetic alteration, prognostic value and gene regulatory networks using multiple databases.

Result

The obtained results showed that MASP2 and DKC1 genes were significantly expressed in advanced UC patients, as well as HNF4A and STAT3 in advanced CD patients.

Conclusion

It can be stated that the biomarker panel MASP2, DKC1, HNF4A, and STAT3 related to them have a significant prognostic role in the candidates of IBD patients for early surgery.

Graphical abstract
Genome-wide CRISPRi Screen in Human iNeurons to Identify Novel Focal Cortical Dysplasia Genes
Authors: Tidball Andrew M. , Luo Jinghui , Clayton Walker J. , Takla Taylor N. , Carvill Gemma L. , Parent Jack M.
Published: December 2023

Focal cortical dysplasia (FCD) is a common cause of focal epilepsy that typically results from brain mosaic mutations in the mTOR cell signaling pathway. To identify new FCD genes, we developed anin vitroCRISPRi screen in human neurons and used FACS enrichment based on the FCD biomarker, phosphorylated S6 ribosomal protein (pS6). Using whole-genome (110,000 gRNAs) and candidate (129 gRNAs) libraries, we discovered 12 new genes that significantly increase pS6 levels. Interestingly, positive hits were enriched for brain-specific genes, highlighting the effectiveness of using human iPSC-derived induced neurons (iNeurons) in our screen. We investigated the signaling pathways of six candidate genes:LRRC4,EIF3A, TSN, HIP1, PIK3R3,andURI1. All six genes increased phosphorylation of S6. However, only two genes,PIK3R3andHIP1,caused hyperphosphorylation more proximally in the AKT/mTOR/S6 signaling pathway. Importantly, these two genes have recently been found independently to be mutated in resected brain tissue from FCD patients, supporting the predictive validity of our screen. Knocking down each of the other four genes (LRRC4, EIF3A, TSN, and URI1) in iNeurons caused them to become resistant to the loss of growth factor signaling; without growth factor stimulation, pS6 levels were comparable to growth factor stimulated controls. Our data markedly expand the set of genes that are likely to regulate mTOR pathway signaling in neurons and provide additional targets for identifying somatic gene variants that cause FCD.

Significance Statement

Focal cortical dysplasia (FCD) is a common cause of focal epilepsy due to somatic variants in mTOR pathway genes in FCD brain tissue. Unbiased sequencing to identify novel FCD genes is challenging since these variants are often in a small subset of neurons. To overcome this challenge, we used anin vitrogenetic screen in human neurons using an FCD biomarker, uncovering genes that increase neuronal mTOR signaling when their expression is lost. Two candidate genes were mutated in patient FCD brain tissues in a recent study, supporting a causative role for these genes in FCD. Our work suggests gene candidates for somatic variant analysis in FCD tissue and indicates added value for genetic screening in neurons over cell lines.
Disease progression and clinical outcomes in latent osteoarthritis phenotypes: Data from the Osteoarthritis Initiative
Authors: Huang Zeyu , Bucklin Mary A. , Guo Weihua , Martin John T.
Published: December 2023

The prevalence of knee osteoarthritis (OA) is widespread and the heterogeneous patient factors and clinical symptoms in OA patients impede developing personalized treatments for OA patients. In this study, we used unsupervised and supervised machine learning to organize the heterogeneity in knee OA patients and predict disease progression in individuals from the Osteoarthritis Initiative (OAI) dataset. We identified four distinct knee OA phenotypes using unsupervised learning that were defined by nutrition, disability, stiffness, and pain (knee and back) and were strongly related to disease fate. Interestingly, the absence of supplemental vitamins from an individual’s diet was protective from disease progression. Moreover, we established a phenotyping tool and prognostic model from 5 variables (WOMAC disability score of the right knee, WOMAC total score of the right knee, WOMAC total score of the left knee, supplemental vitamins and minerals frequency, and antioxidant combination multivitamins frequency) that can be utilized in clinical practice to determine the risk of knee OA progression in individual patients. We also developed a prognostic model to estimate the risk for total knee replacement and provide suggestions for modifiable variables to improve long-term knee health. This combination of unsupervised and supervised data-driven tools provides a framework to identify knee OA phenotype in a clinical scenario and personalize treatment strategies.