bluuebunny/crossref_metadata_2025 huggingface dataset:
Retention of Antibiotic Cement Delivery Implants in Orthopedic Infection Associated with United Fractures Does Not Increase Recurrence Risk
Authors: Ganta Abhishek , Merrell Lauren A. , Adams Jack , Konda Sanjit R. , Egol Kenneth A.
Published: January 2024

OBJECTIVES:

To evaluate if retention of antibiotic cement delivery devices after resolution of orthopedic infection is associated with recurrence.

METHODS:

Design:

Retrospective Cohort

Setting:

Academic Medical Center

Patient Selection Criteria:

Patients with a fracture definitively treated with internal fixation that went on to unite and developed a confirmed fracture-related infection or osteomyelitis following a remote fracture surgery, and had implantation of antibiotic-impregnated cement for infection management.

Outcome Measures and Comparisons: Patients were divided into whom the antibiotic implants were retained (Retained Cohort), and whom the antibiotic implants were removed (Removed Cohort). Outcome measures included: clinical infection resolution, infection recurrence, time to resolution of infection signs, symptoms and laboratory values, reoperation and readmission rates, need for soft tissue coverage (local flap vs free tissue transfer) due to recurrence.

RESULTS:

Of 98 patients treated for FRI in united fractures or osteomyelitis following a remote fracture surgery, 39 (39.8%) underwent implantation of antibiotic-impregnated cement delivery devices: 21 (21.4%) beads, 7 (7.1%) rods, and 11 (11.2%) blocks. Twenty patients (51.3%) comprised the Retained Cohort and 19 patients (48.7%) comprised the Removed Cohort. There were few differences in demographics ([ASA Score, p=0.026] and [Diabetes, p=0.047]), infection location, and pathogenic profiles. The cohorts demonstrated no difference in eventual resolution of infection (100% in the Retained Cohort, 95% in the Removed Cohort, p=0.487) and experienced similar time to clinical infection resolution, based on signs, symptoms and laboratory values (p=0.360). There was no difference in incidence of subsequent infection recurrence following clinical infection resolution (1 recurrence Retained vs 2 recurrences Removed, p=0.605) for those considered “cured”. Compared to the Retained Cohort, the Removed Cohort underwent more reoperations (0.40 vs 1.84 reoperations, p<0.001) and admissions following implantation (p<0.001).

CONCLUSIONS:

Retention of antibiotic-impregnated cement delivery devices in patients with orthopedic infection following fractured bones that have healed was not associated with infection recurrence. Additional surgical intervention with the sole purpose of removing antibiotic delivery devices may not be warranted.
Factors Influencing Medication Administration Outcomes Among New Graduate Nurses Using Bar Code–Assisted Medication Administration
Authors: Sloss Elizabeth A. , Jones Terry L. , Baker Kathy , Robins Jo Lynne W. , Thacker Leroy R.
Published: January 2024

Paramount to patient safety is the ability for nurses to make clinical decisions free from human error. Yet, the dynamic clinical environment in which nurses work is characterized by uncertainty, urgency, and high consequence, necessitating that nurses make quick and critical decisions. The aim of this study was to examine the influence of human and environmental factors on the decision to administer among new graduate nurses in response to alert generation during bar code–assisted medication administration. The design for this study was a descriptive, longitudinal, observational cohort design using EHR audit log and administrative data. The study was set at a large, urban medical center in the United States and included 132 new graduate nurses who worked on adult, inpatient units. Research variables included human and environmental factors. Data analysis included descriptive and inferential analyses. This study found that participants continued with administration of a medication in 90.75% of alert encounters. When considering the response to an alert, residency cohort, alert category, and previous exposure variables were associated with the decision to proceed with administration. It is important to continue to study factors that influence nurses' decision-making, particularly during the process of medication administration, to improve patient safety and outcomes.
Development and Use of a Tech-Based Data Management System for a Cognitive Rehabilitation Randomized Controlled Trial for People With Type 2 Diabetes
Authors: Wood Shenell T. , Cuevas Heather , Kim Jeeyeon , Stuifbergen Alexa K.
Published: January 2024

Successful technology-based interventions to improve patients' self-management are providing an incentive for researchers to develop and implement their own technology-based interventions. However, the literature lacks guidance on how to do this. In this article, we describe the electronic process with which we designed and implemented a technology-based data management system to implement a randomized controlled trial of a comprehensive cognitive rehabilitation intervention to improve cognitive function and diabetes self-management in people with type 2 diabetes. System development included feasibility assessment, interdisciplinary collaboration, design mapping, and use of institutionally and commercially available software. The resulting framework offers a template to support the development of technology-based interventions. Initial development may be time-consuming, but the benefits of the technology-based format surpass any drawbacks.
Health care–related transportation insecurity is associated with adverse health outcomes among adults with chronic liver disease
Authors: Ufere Nneka N. , Lago-Hernandez Carlos , Alejandro-Soto Alysa , Walker Tiana , Li Lucinda , Schoener Kimberly , Keegan Eileen , Gonzalez Carolina , Bethea Emily , Singh Siddharth , El-Jawahri Areej , Nephew Lauren , Jones Patricia , Serper Marina
Published: January 2024

Background:

Health care–related transportation insecurity (delayed or forgone medical care due to transportation barriers) is being increasingly recognized as a social risk factor affecting health outcomes. We estimated the national burden and adverse outcomes of health care–related transportation insecurity among US adults with chronic liver disease (CLD).

Methods:

Using the U.S. National Health Interview Survey from 2014 to 2018, we identified adults with self-reported CLD. We used complex weighted survey analysis to obtain national estimates of health care–related transportation insecurity. We examined the associations between health care–related transportation insecurity and health care–related financial insecurity, food insecurity, self-reported health status, work productivity, health care use, and mortality.

Results:

Of the 3643 (representing 5.2 million) US adults with CLD, 267 [representing 307,628 (6%; 95% CI: 5%–7%)] reported health care–related transportation insecurity. Adults with CLD experiencing health care–related transportation insecurity had 3.5 times higher odds of cost-related medication nonadherence [aOR, 3.5; (2.4–5.0)], 3.5 times higher odds of food insecurity [aOR, 3.5; (2.4–5.3)], 2.5 times higher odds of worsening self-reported health status over the past year [aOR, 2.5; (1.7–3.7)], 3.1 times higher odds of being unable to work due to poor health over the past year [aOR, 3.1; (2.0–4.9)], and 1.7 times higher odds of being in a higher-risk category group for number of hospitalizations annually [aOR, 1.7; (1.2–2.5)]. Health care–related transportation insecurity was independently associated with mortality after controlling for age, income, insurance status, comorbidity burden, financial insecurity, and food insecurity [aHR, 1.7; (1.4–2.0)].

Conclusions:

Health care–related transportation insecurity is a critical social risk factor that is associated with health care–related financial insecurity, food insecurity, poorer self-reported health status and work productivity, and increased health care use and mortality among US adults with CLD. Efforts to screen for and reduce health care–related transportation insecurity are warranted.
HBV infection effects prognosis and activates the immune response in intrahepatic cholangiocarcinoma
Authors: Li Zhizhen , Gao Qingxiang , Wu Yingjun , Ma Xiaoming , Wu Fangyan , Luan Siyu , Chen Sunrui , Shao Siyuan , Shen Yang , Zhang Ding , Feng Feiling , Yuan Lei , Wei Shaohua
Published: January 2024

Background:

The impact of HBV infection on the prognosis of patients with intrahepatic cholangiocarcinoma (ICC) remains uncertain, and the underlying mechanism has not been elucidated. This study aims to explore the potential mechanism via clinical perspectives and immune features.

Methods:

We retrospectively reviewed 1308 patients with ICC treated surgically from January 2007 to January 2015. Then, we compared immune-related markers using immunohistochemistry staining to obtain the gene expression profile GSE107943 and related literature for preliminary bioinformatics analysis. Subsequently, we conducted a drug sensitivity assay to validate the role of TNFSF9 in the ICC organoid-autologous immune cell coculture system and in the patient-derived organoids–based xenograft platform.

Results:

The analysis revealed that tumors in patients without HBV infection exhibited greater size and a higher likelihood of lymphatic metastasis, tumor invasion, and relapse. After resection, HBV-infected patients had longer survival time than uninfected patients (p<0.01). Interestingly, the expression of immune-related markers in HBV-positive patients with ICC was higher than that in uninfected patients (p<0.01). The percentage of CD8+ T cells in HBV-positive tissue was higher than that without HBV infection (p<0.05). We screened 21 differentially expressed genes and investigated the function of TNFSF9 through bioinformatics analyses. The expression of TNFSF9 in ICC organoids with HBV infection was lower than that in organoids without HBV infection. The growth of HBV-negative ICC organoids was significantly inhibited by inhibiting the expression of TNFSF9 with a neutralizing antibody. Additionally, the growth rate was faster in HbsAg (−) ICC patient-derived organoids–based xenograft model than in HbsAg (+) group.

Conclusions:

The activation of the immune response induced by HBV infection makes the prognosis of HBV-positive patients with ICC differ from that of uninfected patients.
Preserflo MicroShunt: Efficacy and Endothelial Cell Density
Authors: Anton Steindor Friedrich , Trigaux Céline , Holtmann Christoph , Spaniol Kristina , Geerling Gerd , Borrelli Maria
Published: January 2024

Précis:

A main safety concern associated with new glaucoma implants is corneal endothelial cell loss, which could even be observed in already established procedures.

Purpose:

The purpose of this study was to evaluate the efficacy and corneal safety, especially corneal endothelial cell loss (ECL), after Preserflo MicroShunt implantation.

Methods:

A monocentric, prospective clinical observational study of patients with a follow-up of at least 12 months who underwent Preserflo MicroShunt implantation at the Department of Ophthalmology, University Hospital of Düsseldorf, Germany, between January 2020 and October 2021. Endothelial cell density (ECD), the distance between the tip of the implant and the corneal endothelium, and the success of the surgery were analyzed.

Results:

In total, 14 eyes of 12 patients were included. After a mean follow-up of 20±2.7 months intraocular pressure was significantly reduced by 8.2 mm Hg (P=0.0041); in 28.6% of patients, a revision surgery was necessary. Reduction of preoperative and follow-up ECD was not statistically significant (ECL of 45 cells/mm2, ECDpreoperative=2074±703.6 cells/mm2, ECDlast follow-up=2029±742.3 cells/mm2, P=0.42). A longer intracameral shunt tube length correlated significantly with a higher distance between the shunt tip and corneal endothelium (r=0.61, P=0.036).

Conclusions:

Preserflo MicroShunt effectively lowered intraocular pressure without substantial ECL after a minimum follow-up period of 17 months.
Air pollution as a potential risk factor for hepatocellular carcinoma in Taiwanese patients after adjusting for chronic viral hepatitis
Authors: Jang Tyng-Yuan , Ho Chi-Chang , Wu Chih-Da , Dai Chia-Yen , Chen Pau-Chung
Published: January 2024

Background:

Air pollution is a risk factor for hepatocellular carcinoma (HCC). However, the effect of air pollution on HCC risk in patients with hepatitis remains unclear.

Methods:

This cross-sectional study recruited 348 patients with chronic hepatitis who were tested for serum hepatitis B surface antigen (HBsAg) and for antibodies against hepatitis B core antigen (HBcIgG) and hepatitis C virus (anti-HCV) in 2022. The diagnosis of HCC was based on the International Classification of Diseases, 10th revision (ICD-10). Daily estimates of air pollutants were aggregated into mean estimates for the previous year based on the date of recruitment or HCC diagnosis.

Results:

Out of 348 patients, 12 had HCC (3.4%). Patients with HCC were older (71.7 vs 50.9 years; p = 0.004), had higher proportion of HBsAg seropositivity (41.7% vs 5.1%; p < 0.001), and substantially higher levels of particulate matter 2.5 (PM2.5) (21.5 vs 18.2 μg/m3; p = 0.05). Logistic regression analysis revealed that the factors associated with HCC were age (odds ratio [OR]: 1.10; CI, 1.03-1.17; p = 0.01), PM2.5 level (OR: 1.51; CI, 1.02-2.23; p = 0.04), and HBsAg seropositivity (OR: 6.60; CI, 1.51-28.85; p = 0.01) (Table 3). There was a combined effect of PM2.5 and HBsAg seropositivity on the risk of HCC development (OR: 22.17; CI, 3.33-147.45; p = 0.001).

Conclusion:

In this study, we demonstrated that PM2.5 and HBsAg seropositivity were associated with HCC occurrence and had synergistic effects after adjusting for confounding factors.
Cost-Effectiveness of Diffusion-Weighted Magnetic Resonance Imaging Versus Second-Look Surgery in Treating Cholesteatoma: A Modeling Study
Authors: Bu Daniel D. , Schwam Zachary G. , Wanna George B. , Perez Enrique , Cosetti Maura K.
Published: January 2024

Objective

To evaluate whether canal wall-up (CWU) tympanomastoidectomy with diffusion-weighted magnetic resonance imaging (DW-MRI) is a cost-effective method of treating cholesteatoma compared with CWU with second-look surgery.

Design and Setting

Cost-effectiveness analysis was conducted using a Markov state transition model. The simulation model adhered to the Panel Recommendations on Cost-Effectiveness in Health and Medicine established by the US Public Health Service. One-way and Monte Carlo probability sensitivity analyses were conducted for validation.

Interventions

Tympanomastoidectomy with DW-MRI versus tympanomastoidectomy with second-look surgery.

Main Outcome Measures

Effectiveness and health utility were measured using quality-adjusted life years (QALYs). Costs were derived from Medicare reimbursement using the perspective of the payer. Probabilities for outcomes and complications were taken from existing literature. Cost-effectiveness was assessed using the incremental cost-effectiveness ratio.

Results

With base case analysis, the total cost was $15,069 when treated with CWU and second-look surgery versus $13,126 when treated with CWU and DW-MRI. The second-look treatment pathway yielded 17.05 QALYs, whereas the DW-MRI pathway yielded 16.91 QALYs in terms of health benefit accrued across the lifetime of the patient. The cost-effectiveness incremental cost-effectiveness ratio was $21,800/QALY. Using the conventional $50,000 willingness-to-pay threshold, second-look surgery was the more cost-effective approach 63.7% of the time by simulation.

Conclusions

Both treatment pathways were found to be cost-effective, with second-look surgery incrementally cost-effective 63.7% of the time. Assumptions were validated by one-way and Monte Carlo probability sensitivity analysis.

Professional Practice Gap and Educational Need

There is ample variation in treatment pathways regarding usage of DW-MRI and second-look surgery for cholesteatoma.

Learning Objective

To evaluate the cost-effectiveness of DW-MRI and second-look surgery approaches, accounting for health-related quality-of-life outcomes and costs for the duration of the patient lifetimes.

Desired Result

To inform the discussion on the treatment for cholesteatoma given emergent noninvasive technologies.

Level of Evidence: Level III.

Indicate IRB or IACUC: Exempt.
Combining Intraoperative Electrocochleography with Robotics-Assisted Electrode Array Insertion
Authors: Kashani Rustin G. , Kocharyan Armine , Bennion Douglas M. , Scheperle Rachel A. , Etler Christine , Oleson Jacob , Dunn Camille C. , Claussen Alexander D. , Gantz Bruce J. , Hansen Marlan R.
Published: January 2024

Objective

To describe the use of robotics-assisted electrode array (EA) insertion combined with intraoperative electrocochleography (ECochG) in hearing preservation cochlear implant surgery.

Study Design

Prospective, single-arm, open-label study.

Setting

All procedures and data collection were performed at a single tertiary referral center.

Patients

Twenty-one postlingually deaf adult subjects meeting Food and Drug Administration indication criteria for cochlear implantation with residual acoustic hearing defined as thresholds no worse than 65 dB at 125, 250, and 500 Hz.

Intervention

All patients underwent standard-of-care unilateral cochlear implant surgery using a single-use robotics-assisted EA insertion device and concurrent intraoperative ECochG.

Main Outcome Measures

Postoperative pure-tone average over 125, 250, and 500 Hz measured at initial activation and subsequent intervals up to 1 year afterward.

Results

Twenty-two EAs were implanted with a single-use robotics-assisted insertion device and simultaneous intraoperative ECochG. Fine control over robotic insertion kinetics could be applied in response to changes in ECochG signal. Patients had stable pure-tone averages after activation with normal impedance and neural telemetry responses.

Conclusions

Combining robotics-assisted EA insertion with intraoperative ECochG is a feasible technique when performing hearing preservation implant surgery. This combined approach may provide the surgeon a means to overcome the limitations of manual insertion and respond to cochlear feedback in real-time.
Prevalence and characteristics of coronary artery fistulas among 20 259 patients undergoing invasive coronary angiography
Authors: Yan Wei , He Ziling , Luo Yong , Huang Weiyi , Zhu Bo , Zhong Yi , Wang Xuefeng
Published: January 2024

Background

Coronary artery fistula (CAF) is a rare coronary anomaly. This study aimed to investigate the prevalence, clinical features, and imaging characteristics of CAF among patients undergoing coronary angiography (CAG).

Method

This was a retrospective study including 20 259 consecutive patients (12 458 were male) who underwent CAG at our institution from September 2018 to March 2023. Electronic angiography records were reviewed, and a total of 86 (0.42%) CAF patients were enrolled and analyzed.

Result

Of the 86 CAF patients, 42 (49%) were male. Thus, the prevalence of CAF for males and females was 0.34% and 0.56%, respectively. Arrhythmia, left ventricular (LV) hypertrophy, LV dilation, and LV systolic dysfunction were observed in 38, 25, 10 and 5 cases, respectively. Among the 86 CAF patients, a total of 117 CAFs were detected. 61 (71%) patients had a single CAF, and the remaining 25 (29%) patients had multiple CAFs. Of the 117 CAFs, the most common origins and terminations were the left anterior descending artery (n = 50) and the pulmonary artery (n = 73), respectively. The CAF diameters were greatly varied, ranging from unmeasurable to 7.8 mm, and 22 (18%) CAFs were larger than 3 mm.

Conclusion

In the present study, the prevalence of CAF was 0.42% with a female predilection. Arrhythmia, LV remodeling and dysfunction were common. Seventy-one percent of patients had a single CAF. The left anterior descending artery and the pulmonary artery were the most common origin and termination of CAFs, respectively. Most CAFs were small, and 18% of CAFs were larger than 3 mm.
The existence of a bidirectional link between ischemic heart disease and fibromyalgia
Authors: Mansour Mahmoud , Ehrenberg Scott , Mahroum Naim , Tsur Avishai M. , Fisher Lior , Amital Howard
Published: January 2024

Study objectives

Fibromyalgia (FM) is one of the most common causes of chronic widespread musculoskeletal pain, but also sleep disturbances, cognitive and psychological disorders. It has been suggested that FM may have a correlation with cardiovascular events. In this study, we aimed to assess the association between FM and ischemic heart disease (IHD).

Methods

A population-based cross-sectional study was conducted utilizing data retrieved from the largest medical records database in Israel, Clalit Health Services. Patients were defined as having FM or IHD when there were at least two such documented diagnoses in their medical records. The occurrence of IHD was compared between FM and age- and sex-frequency-matched healthy controls. A logistic regression model was used to estimate this association following an adjustment for conventional cardiovascular risk factors and depression.

Results

An overall population of 18 598 FM patients and 36 985 age- and gender-matched controls were included in the study. The proportion of IHD amongst FM patients was increased in comparison to controls (9.2% and 6.2%, respectively; P < 0.001). Furthermore, FM demonstrated an independent association with IHD on multivariate analysis (odds ratio [OR], 1.43; 95% confidence intervals [CI], 1.33–1.54; P < 0.0001). Finally, IHD was also found to be independently associated with the diagnosis of FM (OR, 1.40; CI, 1.31–1.51; P < 0.0001).

Conclusion

Our data suggest a bidirectional link between FM and IHD even after the adjustment for conventional cardiovascular risk factors. These findings should be considered when treating patients with either FM or IHD, and their routine interactional screening may be of clinical importance.
Turning Loss Into Legacy
Authors: Westphal Christine G. , Williams Rebecca , Sommer Stephanie
Published: January 2024

Organ, tissue, and eye donations provide opportunities to leave a legacy by saving and/or enhancing the quality of life of others. There has been little published related to tissue or eye donation in hospice/palliative care and few initiatives to facilitate donation among hospice patients/families. Donation myths, gaps in knowledge, and, most significantly, lack of donation referral processes result in missed opportunities for patient/families to consider donation. One donor has the potential to impact 75 lives or more through tissue donation and 2 lives through eye donation. Hospice/palliative care providers can play key roles related to education, advocacy, and collaboration. The support of hospice/palliative care organizations and the local Organ Procurement Organization/Tissue and Eye Recovery Agency are essential for facilitating donation opportunities. This article summarizes current literature, examines legislation and regulations related to donation, presents a case that illustrates an opportunity for hospice community based donation, and shares practices that support donation in hospice/palliative care organizations together with the local Organ Procurement Organization/Tissue and Eye Recovery Agency. This article will hopefully provide the impetus for further study and the development of practices to optimize donation in hospice/palliative care, thus providing more patients and families the opportunity to turn loss into legacy.
Evidence Map of Clinical Practice Guideline Recommendations on Stroke Rehabilitation
Authors: Wei Lili , Shang Wenru , Nan Yaxing , Liu Yuming , Yang Jingyu , Yang Kehu
Published: January 2024

The purpose of this study was to provide an evidence map for explaining research trends and gaps. Four databases and clinical practice guidelines-related Websites were searched up to March 2022. Basic information, methodological quality, reporting quality of clinical practice guidelines, and similar stroke recommendations were extracted. The methodological and reporting quality of stroke clinical practice guidelines were evaluated using the Appraisal of Guidelines Research and Evaluation (second version) instrument and the Reporting Items for Practice Guidelines in Healthcare checklist. The bubble plot format of the evidence map helped visualize the overall quality. Data management and analysis were performed using Excel 2013 and SPSS 22.0 software. A total of 12 clinical practice guidelines, published between 1997 and 2020, were included for in-depth analysis. The identified clinical practice guidelines had a mixed quality and scored poorly in the developmental rigor and applicability domains by Appraisal of Guidelines Research and Evaluation (second version). According to the Reporting Items for Practice Guidelines in Healthcare checklist, field four (clarity of expression) showed the highest (79.2%), and field three (rigor of formulation) secured the lowest (28%) reporting rates. The stroke rehabilitation recommendations primarily focused on organizational management, timing and intensity, rehabilitation and nutritional management of dysphagia, return to work, communication, speech, and language function. This would promote improvement in developing trustworthy clinical practice guidelines for stroke rehabilitation.
Prescription Trends of Opioid and Nonopioid Controlled Prescription Adjunctive Analgesics Before and After Cervical Spinal Surgery
Authors: Shermon Suzanna , Kim Chong
Published: January 2024

Objective

Cervical spine surgery may be needed in those with refractory pain or neurologic deficits to improve outcomes in patients with cervical spine disease. However, consensus varies in the literature on the effect of surgery on opioid use. The objectives of this study were to analyze prescription rates of multiple controlled substances before and after cervical spine surgery and distinguish factors that may have contributed to opioid use after surgery.

Design

This is a retrospective cohort study analyzing prescription trends of various controlled substances in 632 patients who underwent cervical spine surgery from 2019 to 2021.

Results

Opioids have the largest rise in prescriptions at 3- and 6-mo time points after cervical spine surgery. A significant association (P < 0.001) was found between opioid use 1 yr before and 1 yr after cervical spine surgery. Exposure to opioids before surgery (odds ratio = 2.77, 95% confidence interval = 1.43–5.51, P = 0.003) and higher morphine milligram equivalent dose (odds ratio = 1.02, 95% confidence interval =1.01–1.04, P = 0.012) were found to be associated with opioid use after surgery. Significantly more females were prescribed controlled substances (P = 0002).

Conclusions

Higher morphine milligram equivalent dose and opioid exposure before surgery are important factors in predicting postsurgical opioid use.
Inadequacies in Undergraduate Musculoskeletal Education - A Survey of Nationally Accredited Allopathic Medical Programs in Canada
Authors: Peeler Jason , Mann Steve , Orchard Taylor , Yu Jaime
Published: January 2024

Objective

To document the current state of MSK medicine education across nationally accredited undergraduate medical programs.

Design

A cross-sectional survey design was used to gather curricular data on three MSK themes: 1) anatomy education; 2) preclinical education; and 3) clerkship education.

Results

The survey had a 100% response rate with all 14 english language medical schools in Canada responding. The mean time spent teaching MSK anatomy was 29.8 hours (SD ± 13.7, range 12 – 60), with all but one program using some form of cadaveric-based instruction. MSK preclinical curricula averaged 58.0 hours (SD ± 53.4, range 6 - 204), with didactic lectures, case-based learning, and small group tutorials being the most common modes of instruction. Curricular content varied greatly, with only 25% of “core or must-know” MSK topics being covered in detail by all programs. MSK training in clerkship was required by only 50% of programs, most commonly being two-weeks in duration.

Conclusion

Results document the large variability and curricular inadequacies that exist in MSK education across nationally accredited allopathic programs and highlight the need for the identification and implementation of more consistent MSK curricular content and educational standards by all nationally accredited medical programs.
The macronuclear genomic landscape within Tetrahymena thermophila
Authors: Derelle Romain , Verdonck Rik , Jacob Staffan , Huet Michèle , Akerman Ildem , Philippe Hervé , Legrand Delphine
Published: January 2024

The extent of intraspecific genomic variation is key to understanding species evolutionary history, including recent adaptive shifts. Intraspecific genomic variation remains poorly explored in eukaryotic micro-organisms, especially in the nuclear dimorphic ciliates, despite their fundamental role as laboratory model systems and their ecological importance in many ecosystems. We sequenced the macronuclear genome of 22 laboratory strains of the oligohymenophoran Tetrahymena thermophila, a model species in both cellular biology and evolutionary ecology. We explored polymorphisms at the junctions of programmed eliminated sequences, and reveal their utility to barcode very closely related cells. As for other species of the genus Tetrahymena, we confirm micronuclear centromeres as gene diversification centres in T. thermophila, but also reveal a two-speed evolution in these regions. In the rest of the genome, we highlight recent diversification of genes coding for extracellular proteins and cell adhesion. We discuss all these findings in relation to this ciliate’s ecology and cellular characteristics.
Non-canonical induction of autophagy increases adeno-associated virus type 2 (AAV2) transduction efficiency
Authors: Sutter Sereina O. , Jetzer Sarah , Lkharrazi Anouk , Pedersen Sofia , Schraner Elisabeth M. , Vogt Bernd , Büning Hildegard , Fraefel Cornel
Published: January 2024

Adeno-associated virus (AAV) serotypes infect a wide range of cell types, making this member of the parvovirus family a versatile tool in gene therapy. Infection as well as transduction is set in motion by means of specific receptors in conjunction with trafficking pathways, particularly endocytosis, a main cell entry pathway of non-enveloped viruses. Here, we report that efficacy of transduction is enhanced upon treating cells with hyperosmotic sucrose, a known blocker of clathrin-mediated endocytosis, through the non-canonical induction of autophagy. This mechanism of autophagy induction, however, is different from the previously reported AAV2-mediated induction of autophagy, which relies on a canonical, phosphoinositide 3-kinase class III (PI3K-III) complex-dependent pathway and appears to be dependent on the virus intrinsic secreted phospholipase A2 (sPLA2) domain, particularly its catalytic center activity.

IMPORTANCE

Adeno-associated virus (AAV) vectors are among the most frequently applied virus-based delivery vehicles for gene therapy. Lack of pathogenicity for humans, availability of a huge number of AAV serotypes differing in their cellular tropism, and the mainly episomal persistence of AAV vector genomes are clear advantages of these biological nanoparticles. By exploring non-pharmacological inducers of autophagy, we provide evidence for a potent and easy to apply strategy to significantly improve the efficacy of recombinant AAV-based gene delivery in hepatic and structural cells. Besides, our data also demonstrate the importance of autophagy for AAV2 infection and vector-mediated transduction in non-hepatic cells.
Machine Learning Uncovers the Transcriptional Regulatory Network for the Production HostStreptomyces albidoflavus
Authors: Jönsson Mathias , Sigrist Renata , Gren Tetiana , Petrov Mykhaylo Semenov , Marcussen Nils , Svetlova Anna , Charusanti Pep , Gockel Peter , Palsson Bernhard O. , Yang Lei , Özdemir Emre
Published: January 2024

Streptomyces albidoflavusis a popular and genetically tractable platform strain used for natural product discovery and production via the expression of heterologous biosynthetic gene clusters (BGCs). However, its transcriptional regulatory network (TRN) and its impact on secondary metabolism is poorly understood. Here we characterized its TRN by applying an independent component analysis to a compendium of 218 high quality RNA-seq transcriptomes from both in-house and public sources spanning 88 unique growth conditions. We obtained 78 independently modulated sets of genes (iModulons) that quantitatively describe the TRN and its activity state across diverse conditions. Through analyses of condition-dependent TRN activity states, we (i) describe how the TRN adapts to different growth conditions, (ii) conduct a cross-species iModulon comparison, uncovering shared features and unique characteristics of the TRN across lineages, (iii) detail the transcriptional activation of several endogenous BGCs, including surugamide, minimycin and paulomycin, and (iv) infer potential functions of 40% of the uncharacterized genes in theS. albidoflavusgenome. Our findings provide a comprehensive and quantitative understanding of the TRN ofS. albidoflavus, providing a knowledge base for further exploration and experimental validation.

Graphical Abstract
WITHDRAWN: Environmentally-informed functional characterization of a plastid diatom metabolic bridge of mitochondrial origin
Authors: Dorrell Richard G. , Zhang Youjun , Liang Yue , Gueguen Nolwenn , Nonoyama Tomomi , Croteau Dany , Penot Mathias , Adiba Sandrine , Bailleul Benjamin , Gros Valérie , Pierella Karlusich Juan José , Zweig Nathanaël , Fernie Alisdair R. , Jouhet Juliette , Maréchal Eric , Bowler Chris
Published: January 2024

Withdrawal statement

The authors have withdrawn this manuscript due to a duplicate posting of manuscript number BIORXIV/2022/507166. Therefore, the authors do not wish this work to be cited as reference for the project. If you have any questions, please contact the corresponding author. The correct preprint can be found at doi: 10.1101/2022.09.08.507166
MATES: A Deep Learning-Based Model for Locus-specific Quantification of Transposable Elements in Single Cell
Authors: Wang Ruohan , Zheng Yumin , Zhang Zijian , Song Kailu , Wu Erxi , Zhu Xiaopeng , Wu Tao P. , Ding Jun
Published: January 2024

Transposable elements (TEs) are crucial for genetic diversity and gene regulation. Current single-cell quantification methods often align multi-mapping reads to either ‘best-mapped’ or ‘random-mapped’ locations and categorize them at subfamily levels, overlooking the biological necessity for accurate, locus-specific TE quantification. Moreover, these existing methods are primarily designed for and focused on transcriptomics data, which restricts their adaptability to single-cell data of other modalities. To address these challenges, here we introduce MATES, a deep-learning approach that accurately allocates multi-mapping reads to specific loci of TEs, utilizing context from adjacent read alignments flanking the TE locus. When applied to diverse single-cell omics datasets, MATES shows improved performance over existing methods, enhancing the accuracy of TE quantification and aiding in the identification of marker TEs for identified cell populations. This development facilitates the exploration of single-cell heterogeneity and gene regulation through the lens of TEs, offering an effective transposon quantification tool for the single-cell genomics community.
mgikit: Demultiplexing toolkit for MGI fastq files
Authors: Bkhetan Ziad Al , Wang Sen
Published: January 2024

MGI sequencing is reported to be an inexpensive solution to obtain genomics information. There is a growing need for software and tools to analyse MGI’s outputs efficiently.mgikitis a tool collection to demultiplex MGI fastq data and reformat it effectively. The tool and its documentation are available at:https://sagc-bioinformatics.github.io/mgikit/.
Opportunistic screening for coronary artery calcium deposition using chest radiographs – a multi-objective models with multi-modal data fusion
Authors: Jeong Jiwoong , Chao Chieh-Ju , Arsanjani Reza , Ayoub Chadi , Lester Steven J. , Pereyra Milagros , Said Ebram F , Roarke Michael , Tagle-Cornell Cecilia , Koepke Laura M. , Tsai Yi-Lin , Jung-Hsuan Chen , Chang Chun-Chin , Farina Juan M. , Trivedi Hari , Patel Bhavik N. , Banerjee Imon
Published: January 2024

Background

To create an opportunistic screening strategy by multitask deep learning methods to stratify prediction for coronary artery calcium (CAC) and associated cardiovascular risk with frontal chest x-rays (CXR) and minimal data from electronic health records (EHR).

Methods

In this retrospective study, 2,121 patients with available computed tomography (CT) scans and corresponding CXR images were collected internally (Mayo Enterprise) with calculated CAC scores binned into 3 categories (0, 1-99, and 100+) as ground truths for model training. Results from the internal training were tested on multiple external datasets (domestic (EUH) and foreign (VGHTPE)) with significant racial and ethnic differences and classification performance was compared.

Findings

Classification performance between 0, 1-99, and 100+ CAC scores performed moderately on both the internal test and external datasets, reaching average f1-score of 0.66 for Mayo, 0.62 for EUH and 0.61 for VGHTPE. For the clinically relevant binary task of 0 vs 400+ CAC classification, the performance of our model on the internal test and external datasets reached an average AUCROC of 0.84.

Interpretation

The fusion model trained on CXR performed better (0.84 average AUROC on internal and external dataset) than existing state-of-the-art models on predicting CAC scores only on internal (0.73 AUROC), with robust performance on external datasets. Thus, our proposed model may be used as a robust, first-pass opportunistic screening method for cardiovascular risk from regular chest radiographs. For community use, trained model and the inference code can be downloaded with an academic open-source license fromhttps://github.com/jeong-jasonji/MTL_CAC_classification.

Funding

The study was partially supported by National Institute of Health 1R01HL155410-01A1 award.
Recreational and occupational physical activity and risk of adverse events in truncatingMYBPC3founder variant carriers
Authors: Hassanzada Fahima , Jansen Mark , van Lint Freyja H.M. , Bosman Laurens P. , Schmidt Amand F. , Dooijes Dennis , van de Sande Danny , Miah Bristi , van der Crabben Saskia N. , Wilde Arthur A.M. , Lekanne Deprez Ronald H. , de Boer Rudolf A. , Christiaans Imke , Jongbloed Jan D.H. , Jorstad Harald T. , Asselbergs Folkert W. , van Tintelen J. Peter , Baas Annette F. , te Riele Anneline S.J.M.
Published: January 2024

Background

MYBPC3founder variants cause hypertrophic cardiomyopathy (HCM) leading to heart failure (HF) and malignant ventricular arrhythmias (MVA). Exercise is typically regarded a risk factor for disease expression, although evidence is conflicting. Stratifying by type of exercise may discriminate low-from high-risk activities in these patients.

Objective(s)

Evaluate effects of exercise, stratified by high-static and high-dynamic component, on risk of major cardiomyopathy-related events (MCE) and cardiomyopathy penetrance amongMYBPC3founder variant carriers.

Methods

We interviewed 188 carriers (57% male, 43.4±14.8 years) on exercise participation since age ten. Exercise was quantified as metabolic equivalent task (MET)-hours/week before presentation. MCE was defined as a composite of MVA (sustained ventricular tachycardia/fibrillation), HF (HF hospitalizations or transplantation), and septal reduction therapy. Static and dynamic exercise were defined per Bethesda classification. Associations of exercise with MCE and cardiomyopathy penetrance were adjusted for sex and assessed using Cox regression.

Results

Overall, 40 (21%) subjects experienced MCE and 139 (74%) were diagnosed with cardiomyopathy. No association was found for overall physical activity and high-static activity with MCE (p=0.900 overall; p=0.274 high-static) or cardiomyopathy penetrance (p=0.787 overall; p=0.774 high-static). In contrast, high-dynamic activity was associated with MVA (dichotomized at 75thpercentile: adjusted hazard ratio 2.70, 95% confidence interval 1.01-7.24, p=0.049).

Conclusions

Overall exercise participation does not generally increase the risk of adverse events amongMYBPC3founder variant carriers. Nonetheless, an increased risk of MVA was observed among those engaged in the highest quartile of high-dynamic-sports, suggesting that high-level high-intensity exercise activities should be entertained with caution.
SARS-CoV-2 wastewater variant surveillance: pandemic response leveraging FDA’s GenomeTrakr network
Authors: Timme Ruth E. , Woods Jacquelina , Jones Jessica L , Calci Kevin R , Rodriguez Rachel , Barnes Candace , Leard Elizabeth , Craven Mark , Chen Haifeng , Boerner Cameron , Grim Christopher , Windsor Amanda M. , Ramachandran Padmini , Muruvanda Tim , Rand Hugh , Tesfaldet Bereket , Amirzadegan Jasmine , Kayikcioglu Tunc , Walsky Tamara , Allard Marc , Balkey Maria , Bias C. Hope , Brown Eric , Judy Kathryn , Pfefer Tina , Tallent Sandra M , Hoffmann Maria , Pettengill James ,   the GenomeTrakr Laboratory consortium
Published: January 2024

Wastewater surveillance has emerged as a crucial public health tool for population-level pathogen surveillance. Supported by funding from the American Rescue Plan Act of 2021, the FDA’s genomic epidemiology program, GenomeTrakr, was leveraged to sequence SARS-CoV-2 from wastewater sites across the United States. This initiative required the evaluation, optimization, development, and publication of new methods and analytical tools spanning sample collection through variant analyses. Version-controlled protocols for each step of the process were developed and published on protocols.io. A custom data analysis tool and a publicly accessible dashboard were built to facilitate real-time visualization of the collected data, focusing on the relative abundance of SARS-CoV-2 variants and sub-lineages across different samples and sites throughout the project. From September 2021 through June 2023, a total of 3,389 wastewater samples were collected, with 2,517 undergoing sequencing and submission to NCBI under the umbrella BioProject, PRJNA757291. Sequence data were released with explicit quality control (QC) tags on all sequence records, communicating our confidence in the quality of data. Variant analysis revealed wide circulation of Delta in the fall of 2021 and captured the sweep of Omicron and subsequent diversification of this lineage through the end of the sampling period. This project successfully achieved two important goals for the FDA’s GenomeTrakr program: first, contributing timely genomic data for the SARS-CoV-2 pandemic response, and second, establishing both capacity and best practices for culture-independent, population-level environmental surveillance for other pathogens of interest to the FDA.

IMPORTANCE

This manuscript serves two primary objectives. Firstly, it summarizes the genomic and contextual data collected during a Covid-19 pandemic response project, which utilized the FDA’s laboratory network, traditionally employed for sequencing foodborne pathogens, for sequencing SARS-CoV-2 from wastewater samples. Secondly, it outlines best practices for gathering and organizing population-level Next Generation Sequencing (NGS) data collected for culture-free, surveillance of pathogens sourced from environmental samples.
Consistency of automated coronary calcium score and extent of emphysema with different CT scanners and radiation dose protocols in lung cancer screening
Authors: Ledda Roberta Eufrasia , Milanese Gianluca , Balbi Maurizio , Sabia Federica , Valsecchi Camilla , Ruggirello Margherita , Sverzellati Nicola , Marchianò Alfonso Vittorio , Pastorino Ugo
Published: January 2024

Objective

To assess the consistency of automated measurements of coronary artery calcification (CAC) burden and emphysema extent on computed tomography (CT) images acquired with different scanners and radiation dose protocols in a lung cancer screening (LCS) population.

Materials and Methods

The analysis included two LCS cohorts, namedinter-scanner cohort, whose subjects underwent two consecutive screening rounds with two different dual-source CT scanners, andinter-dose cohort, whose subjects underwent a low-dose CT scan and an ultra-low dose CT scan.

Exclusion criteria for CAC measurements were software failure, previous history of CVD and/or of coronary stenting, whereas for emphysema assessment software failure only. CT images were retrospectively analyzed by a fully automated AI software for CAC scoring, using three predefined Agatston score categories (0-99, 100-399, and ≥ 400), and emphysema quantification, using the percentage of low attenuation areas (%LAA). Demographic and clinical data were obtained from the written questionnaire completed by each participant at the first visit.

Agreement for CAC and %LAA categories was measured by the k-Cohen Index with Fleiss-Cohen weights (Kw) and 95% Confidence Interval (CI).

Results

In the inter-scanner cohort, an overlap of CAC strata was observed in 218/245 (90%) volunteers with an almost perfect agreement (Kw= 0.91, 95%CI 0.88-0.95), while an overlap of %LAA strata in 182/256 (71%) volunteers, with a substantial agreement (Kw= 0.70, 95%CI 0.63-0.76). In the inter-dose cohort, an overlap of CAC strata was observed in 275/327 (84%) volunteers, with an almost perfect agreement (Kw= 0.86, 95%CI 0.82-0.90), while an overlap of %LAA strata was found in 204/356 (57%) volunteers, with a moderate agreement (Kw= 0.57, 95%CI 0.51-0.63).

Conclusion

Automated CAC and emphysema quantification showed consistent results when applied on CT images acquired with different scanners and different radiation dose CT protocols in two LCS cohorts.
Substrate-dependent oxidative inactivation of a W-dependent formate dehydrogenase involving selenocysteine displacement
Authors: Vilela-Alves Guilherme , Manuel Rita R. , Viegas Aldino , Carpentier Philippe , Biaso Frederic , Guigliarelli Bruno , Pereira Inês A. C. , Romão Maria João , Mota Cristiano
Published: January 2024

Metal-dependent formate dehydrogenases are very promising targets for enzyme optimization and design of bio-inspired catalysts for CO2reduction, towards novel strategies for climate change mitigation. For effective application of these enzymes, the catalytic mechanism must be fully understood, and the molecular determinants clarified. Despite numerous studies, several doubts persist, namely regarding the role played by the possible dissociation of the SeCys ligand from the Mo/W active site. Additionally, the O2sensitivity of these enzymes must also be understood as it poses an important obstacle for biotechnological applications. Here we present a combined biochemical, spectroscopic, and structural characterization ofDesulfovibrio vulgarisFdhAB (DvFdhAB) when exposed to oxygen in the presence of a substrate (formate or CO2). This study reveals that O2inactivation is promoted by the presence of either substrate and involves forming a new species in the active site, captured in the crystal structures, where the SeCys ligand is displaced from tungsten coordination and replaced by a dioxygen or peroxide molecule. This new form was reproducibly obtained and supports the conclusion that, although W-DvFdhAB can catalyze the oxidation of formate in the presence of oxygen for some minutes, it gets irreversibly inactivated after prolonged O2exposure in the presence of either substrate. These results reveal that oxidative inactivation does not require reduction of the metal, as widely assumed, as it can also occur in the oxidized state in the presence of CO2.