bluuebunny/crossref_metadata_2025 huggingface dataset:
Pharmacological Management of Pulmonary Tuberculosis: A Century of Expert Opinions in Cecil Textbook of Medicine
Authors: Manu Peter , Rogozea Liliana M.
Published: October 2022

Background:

Advances in drug therapy for pulmonary tuberculosis have had an extraordinary impact on the incidence of tuberculosis in the United States in the past century, which has decreased from 113/100,000 persons in 1920 to 2.2/100,000 in 2020. Modern treatments have contributed to a remarkable decrease in hospitalizations and mortality and have had a significant impact on the duration and severity of illness, quality of life, and work potential of affected persons.

Study Question:

What are the milestones of the changes in the expert approach to the pharmacological management of pulmonary tuberculosis in the past century?

Study Design:

To determine the changes in the experts' approach to the management of pulmonary tuberculosis, as presented in a widely used textbook in the United States.

Data Sources:

The chapters describing the management of pulmonary tuberculosis in the 26 editions of Cecil Textbook of Medicine published from 1927 through 2020.

Results:

In the preantibiotic era (1927–1943), the Cecil authors emphasized rest, good food, and fresh air as the treatment pillars for pulmonary tuberculosis. The modern era (1947–1971) recorded the discovery of all the drugs that are still used for the initial treatment, in the following order: streptomycin, para-aminosalicylic acid, isoniazid, pyrazinamide, ethambutol, cycloserine, kanamycin, ethionamide, capreomycin, and rifampin. In the postmodern era (1975–2020), therapeutic advances continued with trials of many drug combinations aimed at ameliorating the duration of treatment, drug resistance adverse effects, and poor the recent addition of fluoroquinolones, bedaquiline, and clofazimine.

Conclusions:

The pharmacological management of tuberculosis has remained archaic until the middle of the 20th century. Fundamental progress occurred in a very short period (1947–1971) and was because of the recognition of the antituberculous effect of many antibiotics and chemotherapy agents. The challenges created by mycobacterial infections resistant to multiple drugs remain and have prompted the addition of new drugs in the past decade.
Postpartum Hemorrhage: A Comprehensive Review of Guidelines
Authors: Giouleka Sonia , Tsakiridis Ioannis , Kalogiannidis Ioannis , Mamopoulos Apostolos , Tentas Ioannis , Athanasiadis Apostolos , Dagklis Themistoklis
Published: October 2022

Importance

Postpartum hemorrhage (PPH) is a common complication of childbirth and the leading cause of maternal deaths worldwide, also associated with important secondary sequelae.

Objective

The aim of this study was to review and compare the most recently published influential guidelines on evaluation, management, and prevention of this severe, life-threatening obstetric complication.

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, the Society of Obstetricians and Gynecologists of Canada, the Network for the Advancement of Patient Blood Management, Hemostasis and Thrombosis in collaboration with the International Federation of Gynecology and Obstetrics, the European Board and College of Obstetrics and Gynecology and the European Society of Anaesthesiology, and the World Health Organization on PPH was carried out.

Results

There is a consensus among the reviewed guidelines that once PPH occurs, it is important to identify the underlying cause (4 T's), estimate the blood loss, and immediately initiate a resuscitation protocol with fluid replacement, blood transfusion, and close monitoring of the woman. In case of uterine atony, all the reviewed medical societies recommend uterine massage, bimanual uterine compression, and administration of uterotonics, although minor discrepancies are observed regarding the optimal regimens. If these measures fail, the use of intrauterine balloon tamponade or other surgical interventions is unanimously recommended. There is also agreement regarding the management of PPH due to retained placenta, placenta accreta, obstetric trauma, uterine rupture or inversion, and acute coagulopathy. Massive transfusion protocols are not consistent in the reviewed guidelines. Finally, all guidelines highlight the importance of the active management of the third stage of labor for the prevention of PPH, suggesting several interventions, with the administration of oxytocin being the criterion standard.

Conclusions

Postpartum hemorrhage is a significant contributor of maternal morbidity and mortality. Thus, the development of consistent international practice protocols for the effective management and prevention of this major complication seems of paramount importance and will hopefully improve obstetric outcomes and especially maternal mortality rate.

Target Audience

Obstetricians and gynecologists, family physicians.

Learning Objectives

After participating in this activity, the learner should be better able to explain the definition of postpartum hemorrhage, as well as the initial maternal evaluation; describe the appropriate management of postpartum hemorrhage; and assess the risk factors and adopt strategies for the prevention of postpartum hemorrhage.
Fetal Omphalocele: Review of Predictive Factors Important for Antenatal Counseling?
Authors: Rieder Wawrzyniec , Maurer Sabine Vasseur , Giannoni Eric , Baud David
Published: October 2022

Importance

Congenital omphalocele is among the most common antenatally diagnosed anomalies. As additional abnormalities are found in majority of cases, antenatal investigations target the search for additional structural anomalies and genetic disorders, including aneuploidy. Antenatal management focuses on the assessment of fetal well-being. Unfortunately, antenatal prediction of postnatal and long-term outcomes represents 2 less well-documented but crucial facets of this pathology. A large part of the prognosis relies on aspects that are difficult to predict such as quality of life, neurological development, and autonomy, which cause significant anxiety in expectant parents.

Objective

This article offers a comprehensive review of antenatal management of omphalocele with a specific focus on predictive factors and long-term outcomes.

Evidence Acquisition, Results

We conducted an extensive literature review targeting management of fetal omphalocele. We had a specific interest in factors predictive of fetal and neonatal outcome as well as long-term consequences of omphalocele. Fetuses with large defects and those containing the liver are at higher risk of having a complicated postnatal course. Neonates may experience pulmonary hypoplasia, pulmonary hypertension, and gastroesophageal reflux. In selected cases, motor and cognitive delay may be present, but the overall life-long prognosis and quality of life is good.

Conclusions and Relevance

A multidisciplinary approach should be encouraged after the diagnosis of fetal omphalocele. In addition to clinical team experience, antenatal counseling should be based on objective and gestational age-dependent criteria and should include long-term outcomes.

Target Audience

Obstetricians and gynecologists, family physicians.

Learning Objectives

After completing this activity, the learner should be better able to propose management of antenatal investigations and fetal surveillance; identify antenatal factors predictive of fetal and neonatal outcomes; and explain the different aspects and currents limitations in knowledge regarding long-term outcomes of omphalocele.
Quality of Life of Children Born With a Congenital Heart Defect
Authors: Derridj Neil , Bonnet Damien , Calderon Johanna , Amedro Pascal , Bertille Nathalie , Lelong Nathalie , Goffinet Francois , Khoshnood Babak , Guedj Romain
Published: October 2022

(Abstracted from J Pediatr 2022;244:148–153)

Congenital heart defects are the most common cause of infant death linked to congenital malformations (CHDs). This group of congenital disorders therefore remains a cause for concern, despite improvements in medical and surgical management that have resulted in higher survival rates.
Early vs Expectant Artificial Rupture of Membranes Following Foley Catheter Ripening: A Randomized Controlled Trial
Authors: Gomez Slagle Helen B. , Fonge Yaneve N. , Caplan Richard , Pfeuti Courtney K. , Sciscione Anthony C. , Hoffman Matthew K.
Published: October 2022

(Abstracted from Am J Obstet Gynecol 2022;226:724.e1–724.e9)

The rate of labor induction is nearly 30% of pregnancies in the United States and rising. Amniotomy is widely used as a safe, inexpensive, and effective labor intervention.
Longitudinal Trends in Case Histories and Rehabilitative Device Assessments at Low Vision Examinations
Authors: Nguyen Jacqueline D. , Tan Steven M. , Azenkot Shiri , Chu Marlena A. , Cooper Emily A.
Published: October 2022

SIGNIFICANCE

Understanding longitudinal changes in why individuals frequent low-vision clinics is crucial for ensuring that patient care keeps current with changing technology and changing lifestyles. Among other findings, our results suggest that reading remains a prevailing patient complaint, with shifting priorities toward technology-related topics.

PURPOSE

This study aimed to understand changes in patient priorities and patient care in low vision over the past decade.

METHODS

We conducted a retrospective study of examination records (2009 to 2019, 3470 examinations) from two U.S. low-vision clinics. Automated word searches summarized two properties of the records: topics discussed during the case history and types of rehabilitative devices assessed. Logistic regression was used to model the effects of examination year, patient age, patient sex, and level of visual impairment.

RESULTS

Collapsing across all years, the most common topic discussed was reading (78%), followed by light-related topics (71%) and technology (59%). Whereas the odds of discussing reading trended downward over the decade (odds ratio, 0.57; P = .03), technology, social interaction, mobility, and driving trended upward (odds ratios, 4.53, 3.31, 2.71, and 1.95; all P's < 0.001). The most frequently assessed devices were tinted lenses (95%). Over time, video magnifier and spectacle assessments trended downward (odds ratios, 0.64 and 0.72; P = .004, 0.04), whereas assessments of other optical aids increased. The data indicate several consistent differences among patient demographics.

CONCLUSIONS

Reading is likely to remain a prevailing patient complaint, but an increase in technology-related topics suggests shifting priorities, particularly in younger demographics. “Low-tech” optical aids have remained prominent in low-vision care even as “high-tech” assistive devices in the marketplace continue to advance.
Cervical Pleuropulmonary Blastoma-like Tumor Associated With DICER1 and TP53 Mutations
Authors: Stolnicu Simona , Bartalis Rolland-Jozsef , Mihut Emilia , Szabo Bela , Da Cruz Paula Arnaud , Ye Qiqi , Parkash Vinita , Weigelt Britta , Soslow Robert A.
Published: October 2022

We describe a very unusual cervical tumor in a 12-yr-old patient with a clinical history indicative of DICER1 syndrome. Morphologic, immunohistochemical, and molecular genetic analysis together helped to diagnose this lesion as a cervical pleuropulmonary blastoma-like tumor, associated with TP53 and DICER1 mutations. The tumor displayed usual histologic features including mixtures of embryonal rhabdomyosarcoma, sarcomatous cartilage, compact blastema, primitive spindle cells and anaplasia, akin to type III pleuropulmonary blastoma, and trabecular and retiform patterns. In addition to expanding the phenotypic spectrum of DICER1-associated conditions, we draw attention to genotype-phenotype correlations in DICER1-associated tumors, particularly as they relate to the discovery of a heritable tumor predisposition syndrome.
Male Partner Opinions of the Dapivirine Vaginal Ring Used During an Open-Label Extension HIV Prevention Trial in KwaZulu-Natal, South Africa
Authors: Morar Neetha S. , Mansoor Leila E. , Naidoo Kalendri , Katz Ariana W. K. , Garcia Morgan , Duma Cebo , Precious Myeni Nqobile Bonakele , Tshbalala Themba , Naidoo Sarita , Montgomery Elizabeth T.
Published: October 2022

Background:

The dapivirine vaginal ring (“the ring”) reduced HIV acquisition by about 35% in phase III trials, with modeling from open-label extension trials estimating 50% HIV protection with consistent use. The ring may be used without male partner knowledge. The Assessment of ASPIRE and HOPE Adherence (AHA) substudy aimed to understand the impact of sociocontextual issues on ring adherence. This subanalysis provides insight into disclosure and male partner influence on ring acceptability.

Methods:

Data were collected using 4 focus group discussions with 18 male partners of phase III trial participants at 2 sites in KwaZulu-Natal, South Africa. Qualitative data were coded, summarized by urban vs. rural location, and analyzed thematically.

Results:

Male partners aged 23–49 years wanted to be informed about the ring use to maintain the trust in their relationships. Their initial response to the ring was characterized by fear due to perceived impact of the ring on their female partner's reproductive system, their penile safety, and that the ring would encourage women to engage in unprotected sex and infidelity. Over time and with information and experience with having a partner who had used the vaginal ring, this fear transformed to support for women to have their own HIV prevention option.

Conclusion:

Male partners supported the ring as an HIV prevention method for women but wanted to be informed about its use. Engaging male partners on female-initiated HIV prevention methods and increased education among rural men may contribute to improved partner support and facilitate women's consistent use.
Individuals' Perceptions of Liver Cirrhosis
Authors: Ghasemniaye Namaghi Shiva , Mohammadi Eesa , Hatami Behzad
Published: October 2022

Liver cirrhosis is a chronic and relatively common disease without a definitive cure in most cases. Few studies have investigated affected individuals perceptions of the disease. This qualitative study aimed to describe the perceptions of individuals (n = 27) with liver cirrhosis toward their disease. Interview data was analyzed using conventional content analysis. Data analysis revealed two main themes: the first theme was “perceived sensitivity to the cirrhosis,” which was characterized by concerns about disease transmission to others, concerns about seeing symptoms as a reason in referring to medical centers, hiding disease from others, feeling remorse or guilt in having disease, and personal beliefs about cause of disease. The second theme was the “perceived severity of the cirrhosis,” which was characterized by feelings of disease exacerbation due to tension and stress, discomfort due to continuation of annoying symptoms, discomfort due to ascites, and fear and hope while waiting for liver transplantation. The findings indicate a perceived threat from liver cirrhosis. Such perceived threats and their characteristics could help nurses and other healthcare providers to be aware of this perception in their care of individuals living with liver cirrhosis.
Tissue plasminogen activator resistance is an early predictor of posttraumatic venous thromboembolism: A prospective study from the CLOTT research group
Authors: Knudson M. Margaret , Moore Hunter B. , Moore Ernest E. , Kornblith Lucy Z. , Kiraly Lazlo N. , McNutt Michelle K. , Wade Charles E. , Bruns Brandon R. , Sauaia Angela
Published: October 2022

BACKGROUND

Venous thromboembolism (VTE) remains a frequent postinjury complication with well established but nonmodifiable risk factors. We hypothesized that fibrinolysis shutdown (SD) as measured by thromboelastography (TEG) would be an independent risk factor for VTE in trauma patients.

METHODS

A subgroup of patients enrolled in the CLOTT-2 (Consortium of Leaders in the Study of Traumatic Thromboembolism 2), multicenter prospective cohort study had kaolin TEG and tissue plasminogen activator (tPA)–TEG data at 12 and 24 hours postadmission. Patients underwent a screening duplex venous ultrasound examination during the first week unless clot was already detected on computed tomography. Injury factors associated with early fibrinolysis SD (defined as kaolin TEG Ly30 ≤0.3%) and/or tPA resistance (tPA-R) (defined as kaolin TEG with tPA 75 ng Ly30 <2.1%) were investigated as was the association of the TEG measurements with the development of VTE.

RESULTS

A total of 141 patients had both TEG measurements at 24 hours, and 135 had both TEG measurements at 12 hours. Shutdown was evident at 12 hours in 71 of 135 (52.6%) patients and in 62 of 141 (44%) at 24 hours. Tissue plasminogen activator resistance was found in 61 of 135 (45.2%) at 12 hours and in 49 of 141 (34.3%) at 24 hours. Factors significantly associated with SD included receiving >4 U of FFP in the first 24 hours, the presence of a major brain injury or pelvic fracture, and the need for major surgery. In contrast, factors significantly associated with early tPA-R included >4 U of red blood cells transfused in the first 24 hours and the presence of a major chest injury or long bone fracture. Deep vein thrombosis was detected in 15 patients and pulmonary clots in 5 (overall VTE rate, 14.2%). Tissue plasminogen activator resistance at 12 hours was found to be an independent risk factor for VTE (hazard ratio, 5.57; 95% confidence interval, 1.39–22.39).

CONCLUSION

Early development of a hypercoagulable state as defined by tPA-R at 12 hours after admission represents a potentially modifiable risk factor for postinjury VTE.

LEVEL OF EVIDENCE

Therapeutic/Care Management; Level II.
Adaptation, personalization and capacity in mental health treatments: a balancing act?
Authors: Bennett Sophie D. , Shafran Roz
Published: October 2022

Purpose of review

There are increasing calls for mental health treatments to be adapted for different groups to maximize their acceptability and benefit to patients. However, adaptations can be costly to develop and evaluate, difficult to implement in routine clinical practice and may reduce service capacity at a time when there is unprecedented unmet need. An alternative method is personalization on an individual level. This review provides an overview of the issues related to personalization and adaptation of mental health interventions.

Recent findings

Several terms have been used to describe changes to existing therapies, these reflect different extents to which existing treatments have been changed. Evidence-based practice and modular therapies allow a level of flexibility within intervention delivery without formal changes and not all changes to therapy should be considered as a new/adapted treatment but instead regarded as ‘metacompetence’. Implementing existing interventions in new contexts is preferable to developing new interventions in many instances. New guidance outlines how researchers can adapt and transfer interventions to varied contexts.

The review provides proposed definitions of different changes to therapy. Modified and personalized treatments may improve acceptability to patients whilst maximizing implementation of evidence-based practice within clinical services.
Escherichia coli harbouring strAB with reduced susceptibility towards gentamicin and amikacin: a single centre study from India
Authors: Wangkheimayum Jayalaxmi , Phonglo Prynali , Singha K. Melson , Chanda Debadatta Dhar , Bhattacharjee Amitabha
Published: October 2022

In this study we report the presence of streptomycin resistance gene strAB within clinical isolates of

Escherichia coli

where streptomycin is not used to treat Gram-negative infections. In total, 135

E. coli

isolates were obtained for the study. PCR based detection of strAB was performed in the study isolates followed by assessment of horizontal transferability. Cloning of strAB was done in laboratory strain

E. coli

DH5α. Pre-cloning and post-cloning susceptibility of the strain was done for assessment of acquired resistance. Among tested isolates, 89 were found to harbour strAB and it was encoded within a IncI1 type plasmid. Cloning experiments revealed the strAB gene showed unusual non-susceptibility towards amikacin and gentamicin. The study highlighted that strAB, which has a role in streptomycin resistance, may also have a role in reduced susceptibility towards gentamicin and amikacin within a clinical setting.
Pseudomonas aeruginosa LasR overexpression leads to a RsaL-independent pyocyanin production inhibition in a low phosphate condition
Authors: Soto-Aceves Martín Paolo , González-Valdez Abigail , Cocotl-Yañez Miguel , Soberón-Chávez Gloria
Published: October 2022

Several

Pseudomonas aeruginosa

virulence-related traits like pyocyanin are regulated by an intricate regulatory network called quorum sensing (QS) that relies on transcriptional regulators that are activated through binding to a self-produced molecule called an autoinducer (AI). QS is composed of three systems, Las, Rhl and Pqs. In the Las system, the regulatory protein LasR interacts with its AI to activate the other two QS systems. In turn, the Rhl and Pqs systems regulate the expression of multiple virulence-related genes, such as the genes of the reiterated operons phzA1B1C1D1E1F1G1 and phzA2B2C2D2E2F2G2 involved in pyocyanin production. The Las system also regulates the negative regulator RsaL, which provides negative feedback to the QS-response, including repression of pyocyanin synthesis genes. In this work, we describe that LasR can act as a negative regulator of phzA1 transcription and hence of pyocyanin production and that this regulation is independent of RsaL activity. This work contributes to the understanding of QS-dependent pyocyanin production and demonstrates a previously uncharacterized role of LasR as a repressor.
Asthma and the Risk of SARS-CoV-2 Infection Among Children and Adolescents
Authors: Rao Saahithi , Hurst Jillian H , Zhao Congwen , Goldstein Benjamin A. , Thomas Laine , Lang Jason E. , Kelly Matthew S
Published: October 2022

Importance: More than 4 million SARS-COV-2 infections have occurred among children and adolescents in the United States. Risk factors for SARS-CoV-2 infection among children remain poorly defined. Objective: To evaluate the association between asthma and the risk of SARS-CoV-2 infection among children. Design: Retrospective cohort study Setting: A large, integrated health system in central North Carolina. Participants: Children 5 to 17 years of age with a Durham County address and at least one health care encounter in the Duke University Health System between March 1, 2017, and February 28, 2020. Exposure: Diagnosis of asthma Main Outcomes and Measures: The primary outcome was SARS-CoV-2 infection identified by PCR testing of a respiratory sample collected between March 1, 2020, and October 31, 2020. We matched children with asthma 1:1 to children without asthma using propensity scores and used Poisson regression to evaluate the association between asthma and the risk of SARS-CoV-2 infection. We assessed for effect modification of this association by inhaled corticosteroid prescription and comorbid atopic diseases. Results: Of 49,455 children, 6,515 (13%) met criteria for a diagnosis of asthma; all children with asthma were matched to a control child without asthma for a final cohort of 13,030 children. Median (interquartile range) age was 11.0 (8.0, 14.0) years, 56% were male, and 78% were non-White. A diagnosis of asthma was associated with a decreased risk of SARS-CoV-2 infection [risk ratio (RR): 0.67, 95% confidence interval (CI): 0.49-0.92]. This association tended to be stronger in children with asthma who were prescribed inhaled corticosteroids (RR: 0.60, 95% CI: 0.38-0.94) or who had comorbid atopic diseases (RR: 0.59, 95% CI: 0.39-0.88). Of the 66 children with asthma who developed SARS-CoV-2 infection, none required hospitalization for COVID-19. Conclusions and Relevance: Children with asthma had a lower risk of SARS-CoV-2 infection, particularly children prescribed an inhaled corticosteroid or with comorbid atopic diseases. Further studies are needed to explore the complex relationship between asthma, inhaled corticosteroids, and SARS-CoV-2.
An Evaluation of The Regional Distribution of Pediatric Surgery Workforce and Surgical Load in Brazil
Authors: Bustorff-Silva Joaquim , Miranda Márcio Lopes , Rosendo Amanda , de Oliveira Filho António Gonçalves
Published: October 2022

Aim

The purpose of this study is to present data on the regional distribution of the pediatric surgical workforce and the expected local demand of pediatric operations in Brazil.

Methods

We collected data on the pediatric surgical workforce, surgical workload, GDP/capita and mortality for gastrointestinal tract malformations (MGITM) across the different regions of Brazil for 2019.

Findings

Data from CFM reported the existence of 1515 pediatric surgery registries in Brazil, corresponding to 1414 individual pediatric surgeons (some pediatric surgeons are registered in more than one State), or 2.4 pediatric surgeons per 100.000 children< 14 years. There were 828 male and 586 female with a M/F ratio of 1.14:1. Mean age was 51.5±12.8 years and mean time from graduation was 3,4±5,7years. Regional distribution showed a higher concentration of pediatric surgeons on the wealthier Central-West, South and Southeast regions. Individual workload ranged from 88 to 245 operations/year (average 146 operations/year) depending on the region. Only 9 (6.1%) of these were high complexity (including neonatal) operations. MGITM tended to be higher on the poorer North and Northeast regions of Brazil

Conclusions

We found wide disparities in the surgical workforce and workload across Brazil, related to socioeconomic status. Areas of increased surgical workforce were associated with lower MGITM. The average number of complex operations performed yearly by the individual pediatric surgeon was considerably low. Strategic investment and definition of health policies may be needed to improve the quality of care in the different regions of Brazil.

Level of Evidence

Retrospective review. Level III
Structural models of genome-wide covariance identify multiple common dimensions in autism
Authors: de Hoyos Lucía , Barendse Maria T , Schlag Fenja , van Donkelaar Marjolein MJ , Verhoef Ellen , Shapland Chin Yang , Klassmann Alexander , Buitelaar Jan , Verhulst Brad , Fisher Simon E , Rai Dheeraj , Pourcain Beate St
Published: October 2022

Common genetic variation has been associated with multiple symptoms in Autism Spectrum Disorder (ASD). However, our knowledge of shared genetic factor structures contributing to this highly heterogeneous neurodevelopmental condition is limited. Here, we developed a structural equation modelling framework to directly model genome-wide covariance across core and non-core ASD phenotypes, studying autistic individuals of European descent using a case-only design. We identified three independent genetic factors most strongly linked to language/cognition, behaviour and motor development, respectively, when studying a population-representative sample (N=5,331). These analyses revealed novel associations. For example, developmental delay in acquiring personal-social skills was inversely related to language, while developmental motor delay was linked to self-injurious behaviour. We largely confirmed the three-factorial structure in independent ASD-simplex families (N=1,946), but uncovered simplex-specific genetic overlap between behaviour and language phenotypes. Thus, the common genetic architecture in ASD is multi-dimensional and contributes, in combination with ascertainment-specific patterns, to phenotypic heterogeneity.
Whole-brain structural and functional neuroimaging of individuals who attempted suicide and people who did not: a systematic review, exploratory coordinate-based meta-analysis and seed-based connectivity study
Authors: Meda Nicola , Miola Alessandro , Cattarinussi Giulia , Sambataro Fabio
Published: October 2022

Introduction

Suicide is the cause of death of approximately 800’000 people a year. Despite the relevance of this behaviour, risk assessment tools rely on clinician experience and subjective ratings.

Methods

Given that previous suicide attempts are the single strongest predictors of future attempts, we designed a systematic review and coordinate-based meta-analysis to evince if any neuroimaging features can help distinguish individuals who attempted suicide from subjects who did not. Out of 5659 publications from PubMed, Scopus and Web of Science, we summarised 102 experiments and meta-analysed 23 of them.

Results

A cluster in the right Superior Temporal Gyrus, a region implicated in emotional processing, might be functionally hyperactive in individuals who attempted suicide. Furthermore, we used JuSpace and the Human Brain Connectome dataset to show that this cluster is enriched in 5-HT1Aheteroreceptors, and its connectivity with the left central operculum is significantly correlated with loneliness scores.

Conclusions

This evidence provides a putative neural substrate for suicidal thought-to-attempt transition as hypothesised by Joiner’s Interpersonal Theory of Suicide. Heterogeneity in the analytical techniques and weak or absent power analysis of the studies included in this review currently limit the applicability of the findings, the replication of which should be prioritised.
Initial Insights from a Quality Improvement Initiative to Develop an Evidence-informed Young Adult Substance Use Program
Authors: Halladay Jillian , Stead Victoria , McCarron Catherine , Kennedy Marina , King Kyla , Venantius Michelle , Carter A. , Syan Sabrina , Matthews Mareena , Khoshroo Saba , Massey Myra , Rahman Liah , Burns Jacinda , Punia Kiran , MacKillop Emily , Raymond Holly , MacKillop James
Published: October 2022

Background

High rates of substance misuse during emerging adulthood require developmentally appropriate clinical programs.

Objectives

This work outlines the development of an evidence-informed emerging adult outpatient substance use program, quality improvement process and protocol, and 1-year program insights.

Methods

Literature reviews, program reviews, environmental scans, and stakeholder consultations (including lived expertise) were used to develop the program. A 12-week emerging adult (17-25) measurement-based care program was developed including: 1) individual measurement-based care and motivational enhancement therapy sessions; 2) group programming focused on cognitive behavioural therapy, mindfulness, distress tolerance, and emotional regulation; 3) consults for diagnostic clarification and/or medication review; and 4) a separate education group for loved ones. A measurement system was concurrently created to collect clinical and program evaluation data at 6 time points.

Results

In the first year of the program, 96 young adults fully enrolled in the program (Mean age = 21 years old, 48% female gender) primarily reporting treatment targets of alcohol (70%) and cannabis (59%). Almost all patients (97%) surpassed at least one clinical threshold for co-occurring mental health disorder, with the median/mode of positive psychiatric screens being for 5 conditions.

Conclusions

This program demonstrates that developing an integrative evidence-informed measurement-based care young adult substance use program is feasible, though requires flexibility and ongoing monitoring to meet local needs. Patient characteristics reveal very high rates of concurrent psychiatric disorders in addition to substance use disorders.
Prediction of clinically relevant postoperative pancreatic fistula using radiomic features and preoperative data
Authors: Bhasker Nithya , Kolbinger Fiona R. , Skorobohach Nadiia , Zwanenburg Alex , Löck Steffen , Weitz Jürgen , Hoffmann Ralf-Thorsten , Distler Marius , Speidel Stefanie , Leger Stefan , Kühn Jens-Peter
Published: October 2022

Clinically relevant postoperative pancreatic fistula (CR-POPF) can significantly affect the treatment course and outcome in pancreatic cancer patients. Preoperative prediction of CR-POPF can aid the surgical decision-making process and lead to better perioperative management of patients. In this retrospective study of 108 pancreatic head resection patients, we present risk models for the prediction of CR-POPF that use combinations of preoperative computed tomography (CT)-based radiomic features, mesh-based volumes of annotated intra- and peripancreatic structures and preoperative clinical data. The risk signatures were evaluated and analysed in detail by visualising feature expression maps and by comparing significant features to the established CR-POPF risk measures. Out of the risk models that were developed in this study, the combined radiomic and clinical signature performed best with an average area under receiver operating characteristic curve (AUC) of 0.86 and a balanced accuracy score of 0.76 on validation data. The following pre-operative features showed significant correlation with outcome in this signature (p<0.05)- texture and morphology of the healthy pancreatic segment, intensity volume histogram-based feature of the pancreatic duct segment, morphology of the combined segment, and BMI. The predictions of this pre-operative signature showed strong correlation (Spearman correlation co-efficient,ρ= 0.7) with the intraoperative updated alternative fistula risk score (ua-FRS), which is the clinical gold standard for intraoperative CR-POPF risk stratification. These results indicate that the proposed combined radiomic and clinical signature developed solely based on preoperatively available clinical and routine imaging data can perform on par with the current state-of-the-art intraoperative models for CR-POPF risk stratification.
A novel cuproptosis-related gene signature for the prediction of liver cancer prognosis identified DLAT is a potential therapeutic target
Authors: Xu Dong , Yang Fei , Chen Yang , Zhu Hong , Sun Haijian , Shen Tong , Zhu Yongkang , Zhou Guowei , Chen Dexuan , Yang Xiaojun , Lin Kai , Xia Cunbing
Published: October 2022

Background and Purpose

The liver cancer (LC) is a highly malignant tumor of the digestive system with a poor prognosis. Cuproptosis is a new type of regulated cell death that has been found by researchers. The expression of cuproptosis-related genes in LC and their relevance to prognosis, on the other hand, remain unknown. This study aimed to explore a gene signature to predict the liver cancer prognosis and identified the vital gene.

Experimental approach

The expression patterns of RNA and related clinical data of 371 LC patients were obtained based on The Cancer Genome Atlas (TCGA). Differentially expressed genes (DEGs) were acquired by comparing tumors with adjacent normal samples. Genes displaying significant association with OS were screened through univariate Cox regression analysis and the least absolute shrinkage and selection operator (LASSO) algorithm. All cases were classified into the validation or training group to validate the constructed gene signature. We conducted real-time polymerase chain reaction (PCR) and assays for transwell invasion, CCK-8, and colony formation to determine the biological roles of DLAT.

Key Results

The differential expression of twelve cuproptosis regulators in LC and normal liver tissues was discovered in this investigation. DEGs can be used to distinguish between two forms of LC. Cuproptosis-related genes were evaluated for survival predictive significance using the Cancer Genome Atlas (TCGA) cohort. A 3-gene signature based on least absolute shrinkage and selection operator (LASSO) Cox regression was used to categorize an LC patient cohort from the TCGA into low- and high-risk categories. Patients in the low-risk group had a considerably higher likelihood of surviving (P = 0.05) than those in the high-risk group. When paired with clinical parameters, risk score was an independent predictor in predicting the OS of patients with LC.

Conclusions & Implications

Cuproptosis-related genes thus play an important role in tumor formation and can be used to predict the prognosis of LC patients. DLAT has the best prognostic value and can be a therapeutic target for liver cancer.
Age-dependent topic modelling of comorbidities in UK Biobank identifies disease subtypes with differential genetic risk
Authors: Jiang Xilin , Zhang Martin Jinye , Zhang Yidong , Durvasula Arun , Inouye Michael , Holmes Chris , Price Alkes L. , McVean Gil
Published: October 2022

The analysis of longitudinal data from electronic health records (EHR) has potential to improve clinical diagnoses and enable personalised medicine, motivating efforts to identify disease subtypes from age-dependent patient comorbidity information. Here, we introduce an age-dependent topic modelling (ATM) method that provides a low-rank representation of longitudinal records of hundreds of distinct diseases in large EHR data sets. The model learns, and assigns to each individual, topic weights for several disease topics, each of which reflects a set of diseases that tend to co-occur within individuals as a function of age. Simulations show that ATM attains high accuracy in distinguishing distinct age-dependent comorbidity profiles. We applied ATM to 282,957 UK Biobank samples, analysing 1,726,144 disease diagnoses spanning all 348 diseases with ≥1,000 independent occurrences in the Hospital Episode Statistics (HES) data, identifying 10 disease topics under the optimal model fit. Analysis of an independent cohort, All of Us, with 211,908 samples and 3,098,771 disease diagnoses spanning 233 of the 348 UK Biobank diseases produced highly concordant findings. In UK Biobank we identified 52 diseases with heterogeneous comorbidity profiles (≥500 occurrences assigned to each of ≥2 topics), including breast cancer, type 2 diabetes (T2D), hypertension, and hypercholesterolemia. For most of these diseases, topic assignments were highly age-dependent, suggesting differences in disease aetiology for early-onset vs. late-onset disease. We defined subtypes of the 52 heterogeneous diseases based on the topic assignments, and compared genetic risk across subtypes using polygenic risk scores (PRS). We identified 18 disease subtypes whose PRS differed significantly from other subtypes of the same disease, including a subtype of T2D characterised by cardiovascular comorbidities and a subtype of asthma characterised by dermatological comorbidities. We further identified specific variants underlying these differences such as a T2D-associated SNP in theHMGA2locus that has a higher odds ratio in the top quartile of cardiovascular topic weight (1.18±0.02) compared to the bottom quartile (1.00±0.02) (P=3 × 10-7for difference, FDR = 0.0002 < 0.1). In conclusion, ATM identifies disease subtypes with differential genome-wide and locus-specific genetic risk profiles.
IMPROVING CARDIOVASCULAR DISEASE RISK PREDICTION WITH MACHINE LEARNING USING MENTAL HEALTH DATA: A PROSPECTIVE UK BIOBANK STUDY
Authors: Dorraki Mohsen , Liao Zhibin , Abbott Derek , Psaltis Peter J. , Baker Emma , Bidargaddi Niranjan , Wardill Hannah R. , van den Hengel Anton , Narula Jagat , Verjans Johan W.
Published: October 2022

Background

Robust and accurate prediction of cardiovascular disease (CVD) risk facilitates early intervention to benefit patients. It is well-known that mental disorders and CVD are interrelated. Nevertheless, psychological factors are not considered in existing models, which use either a limited number of clinical and lifestyle factors, or have been developed on restricted population subsets.

Objectives

To assess whether inclusion of psychological data could improve CVD risk prediction in a new machine learning (ML) approach.

Methods

Using a comprehensive, long-term UK Biobank dataset (n=375,145), we examined the correlation between CVD diagnoses and traditional and psychological risk factors. An ensemble ML model containing five constituent algorithms [decision tree, random forest, XGBoost, support vector machine (SVM), and deep neural network (DNN)] was tested for its ability to predict CVD risk based on two training datasets: one using traditional CVD risk factors alone, or a combination of traditional and psychological risk factors.

Results

Our ensemble ML model could predict CVD with 71.31% accuracy using traditional CVD risk factors alone. However, by adding psychological factors to the training data, accuracy dramatically increased to 85.13%. The accuracy and robustness of our ensemble ML model outperformed all five constituent learning algorithms. Re-testing the model on a control dataset to predict bone diseases returned random results, confirming specificity of the training data for prediction of CVD.

Conclusions

Incorporating mental health assessment data within an ensemble ML model results in a significantly improved, highly accurate, state-of-the-art CVD risk prediction.

AUTHOR APPROVAL

All authors have seen and approved the manuscript.

COMPETING INTERESTS

The authors declare no competing interests.

DATA AVAILABILITY STATEMENT

All data needed to evaluate the conclusions in the paper are present in the paper or in the supplementary materials. In addition, we used UK Biobank in this study:www.ukbiobank.ac.uk.

FUNDING

No funding.
CNA Explorer and anaLyzer (CNAEL): an interactive web application and standard operating procedure enabling efficient clinical review and reporting of complex NGS-derived tumor copy number profiles
Authors: Chen Ellen , Wang Jinlian , Kueffner Robert , Al-Kateb Hussam , Silkov Antonina , Uzilov Andrew , Lochovsky Lucas , Li Hui , Newman Scott
Published: October 2022

Purpose

Clinical analysis and reporting of somatically acquired copy number abnormalities (CNAs) detected through next-generation sequencing (NGS) is time consuming and requires significant expertise. Interpretation is complicated by other classes of variants such as coding mutations and gene fusions. Recent guidelines for the clinical assessment of tumor CNAs harmonize and simplify the reporting criteria but did not directly address NGS-specific concerns or the need for a standardized and scalable protocol for CNA analysis.

Methods

We developed a scalable NGS-derived CNA analysis protocol paired with a novel interactive web application, CNA Explorer and anaLyzer (CNAEL), to facilitate the rapid, scalable, and reproducible analysis and reporting of complex tumor-derived CNA profileshttps://CNAEL.sema4.com.

Results

Novel features of CNAEL include on-the-fly data rescaling to account for tumor ploidy, purity, and modal chromosomal copy number; integration of gene expression, coding, and fusion variants into review and automated genome-wide summarization to enable rapid reporting. We found that case curation times were significantly reduced when using CNAEL [median:7 mins, IQR = 4, 10.25] compared with our previous laboratory standard operating procedure [median: 61 mins, IQR = 23.75, 176,25] with p=4.631e-05.

Conclusion

CNAEL enables efficient and accurate clinical review and reporting of complex NGS-derived tumor copy number profiles.
Responsiveness of the electrically stimulated cochlear nerve in patients with a missense variant inACTG1: Preliminary Results
Authors: Yuan Yi , Yan Denise , Skidmore Jeffrey , Chapagain Prem , Liu Xuezhong , He Shuman
Published: October 2022

Objectives

This preliminary study identified a missense variant inACTG1(NM_001614.5) in a family with autosomal dominant non-syndromic hearing loss (ADNSHL). The responsiveness of the electrically-stimulated cochlear nerve (CN) in two implanted participants with this missense change was also evaluated and reported.

Design

Genetic testing was done using a custom capture panel (MiamiOtoGenes) and whole exome sequencing. The responsiveness of the electrically-stimulated CN was evaluated in two members of this family (G1 and G4) using the electrically evoked compound action potential (eCAP). eCAP results from these two participants were compared with those measured three implanted patient populations: children with cochlear nerve deficiency, children with idiopathic hearing loss and normal-sized cochlear nerves, and postligually deafened adults.

Results

Sequencing ofACTG1identified a missense c.737A>T (p. Gln246Leu) variant inACTG1(NM_001614.5) which is most likely the genetic cause of ADNSHL in this family. eCAP results measured in these two participants showed substantial variations.

Conclusion

The missense c.737A>T (p. Gln246Leu) variant inACTG1(NM_001614.5) co-segregated with hearing loss in this family. The responsiveness of the electrically-stimulated CN can vary among patients with the same genetic variants, which suggests the importance of evaluating the functional status of the CN for individual CI patients.
A comparison of claw removal methods on the post-release survival and claw regeneration of stone crab (Menippe mercenaria)
Authors: Walus Alexandria M. , Schneider Eric V. C. , Parker Erin , Brittain Candice , McGaw Iain J. , Hayes Daniel , Peters Amber , Van Leeuwen Travis E.
Published: October 2022

Commercial and recreational stone crab (Menippe mercenaria) fisheries primarily occur along the Gulf of Mexico and Atlantic coasts of the southeastern United States and the northeastern Caribbean. The fishery is unique in that only the crabs’ claws are retained and the animal is returned to the water alive. While the fishery is often regarded as sustainable because it is believed to exploit the crabs’ natural ability to voluntarily drop (autotomize) and regenerate lost claws, the post-release survival of de-clawed stone crabs is often low, especially when both claws are harvested. In this study, a controlled laboratory experiment was used to compare a new method of claw removal to the typical method currently used in the fishery. For the two different claw removal methods, we compared crab survival and start time to claw regeneration as a function of harvester and whether one claw or both claws were removed. Overall, we found a significant effect of the removal method, harvester, and whether one claw or both claws were removed on crab survival, but these factors did not influence the time to start of claw regeneration. Although our new method was several seconds slower in processing time than the typical method, it resulted in a 28% increase in survival (up to 92% survival throughout the study) compared to the typical method of claw removal (64% survival throughout the study). Overall, these results suggest that our new method of claw removal significantly increases post-release survival of stone crabs, and most notably does so independent of harvester and whether one claw or both claws are removed.