bluuebunny/crossref_metadata_2025 huggingface dataset:
An Elusive Diagnosis: Delays in Treatment and Opportunities for Improvement in Temporal Encephalocele and CSF Leak
Authors: Curry Steven D. , McCorkle Colin E. , Hatch Jonathan L. , Casazza Geoffrey C.
Published: February 2023

Objective:

Symptoms of temporal encephalocele or cerebrospinal fluid (CSF) leak causing middle ear effusion or otorrhea can be nonspecific and mistaken for other common diagnoses, leading to delays in diagnosis, failed treatments, and a risk of meningitis. This study sought to investigate the association between symptomatology and time to definitive surgical management.

Study Design:

Retrospective cohort.

Setting:

Single tertiary care academic medical center.

Patients:

Adults treated surgically for temporal encephalocele or CSF leak. Revision cases were excluded.

Interventions:

Chart review was performed to identify pertinent symptoms at presentation. Multivariable regression was performed to analyze the association between symptoms and time to definitive management.

Main Outcome Measures:

Otologic and related symptoms present prior to middle cranial fossa (MCF). Time between symptom onset and surgical treatment.

Results:

Thirty-four patients had symptoms present a median of 15.5 months (interquartile range, 8–35 months; range, 1 month to 12 years) prior to surgery. The most common symptoms were subjective hearing loss in the affected ear (76.5%) and aural fullness (73.5%). Otorrhea was present in 55.9%, and 42.9% had a history of otorrhea after myringotomy with or without tube insertion. Meningitis occurred in 5 patients (14.7%). Only the absence of otalgia was statistically significantly associated with decreased time between symptoms onset and surgery (P = 0.01).

Conclusions:

Encephalocele and CSF leak were most commonly associated with aural fullness and hearing loss. Medical treatment for presumed Eustachian tube dysfunction or chronic ear disease were commonly observed. Patients had symptoms for a median of almost 1 and a half years prior to surgical management.
Beliefs and perspectives on the future of oncology pharmacy—collated results of member surveys of the European Society of Oncology Pharmacy
Authors: Crul Mirjam , Meier Carolin , Meier Klaus
Published: February 2023

Introduction:

The European Society of Oncology Pharmacy (ESOP) has nearly 4000 members in 66 countries. Periodically, the needs and interests of the members as well as the predictions of the members for the development of the profession of oncology pharmacy are mapped by the board of the Society. The aim of these inquiries is to help focus the Societies' advocacy works, knowledge exchange, and scientific and educational programs into those areas where the members deem this most needed.

Methods:

One survey into the future of oncology pharmacy was held in 12 individual countries during a national meeting on the topic of oncology pharmacy. In this survey, the forecasts of the members were researched. A second survey was held under the full membership to identify the topics of most interest within the broader field of oncology care.

Results:

Five hundred ninety-five colleagues responded to the future of oncology pharmacy survey and 757 to the topics of interest survey. Participating respondents came from 53 individual countries. Combined, the results show that both clinical care (in multiprofessional treatment teams) and education are important areas for the Society to continue paying attention to. The other important aspect of oncology pharmacy, which includes the practical and safety aspects of compounding, remains of great interest, especially regarding technical innovations such as robotics.

Conclusion:

ESOP will remain focused on its initial aim: to support optimal treatment for patients with cancer. The globally collated data from the two surveys show that both the clinical and the practical sides of the profession deserve continuing advancement.
A qualitative exploration of the lived experiences and perceived impact of a supportive-expressive group therapy on men living with gastrointestinal cancer
Authors: Martopullo Celestina , Oberoi Devesh V. , Carlson Linda E. , Bultz Barry D.
Published: February 2023

Background:

This study seeks to understand the functioning of a gastrointestinal (GI) men-only Supportive-Expressive Group Therapy (SEGT) program over time by exploring (1) men's lived experiences with group process and (2) perceived group impact relevant to supportive/expressive goals.

Methods:

A convenience sample of patients with GI cancer attending an ongoing, men-only GI cancer SEGT was interviewed at 3 and 6 months from enrollment. A qualitative study design with mixed inductive and framework thematic analysis was used. Open-ended, semistructured interviews directed the exploration of group experiences over time. SEGT goals framed the inquiry toward exploring the perceived impact of the group.

Results:

Twenty-three men were interviewed at 3 months and 13 men at 6 months of intervention. Men pointed to an overall global satisfaction with group process and subjects discussed. The SEGT model provided a sex sensitive, safe, and mutually supportive outlet for expressing and normalizing participants' feelings and emotions. Three central themes emerged relevant to group experiences: (1) the role of social comparison, (2) the role of supportive-expressive exchanges, and (3) the role of the group format, composition, and facilitation. Feeling heard and validated accelerated a sense of belonging and facilitated emotional disclosure. SEGT contributed to re-evaluation of life values/goals, mitigation of existential anxiety, and mood improvement.

Conclusions:

Group participants perceived the SEGT as effective in addressing and mitigating emotional and existential concerns. Perceived benefits were consistent with SEGT goals. The findings offer groundwork for developing men-centered cancer support groups that foster emotional exploration and expressive disclosure through validation and acceptance.
Immunohistochemical Detection of 5T4 in Renal Cell Carcinoma
Authors: Miller Christopher P. , Shokri Farinaz , Akilesh Shreeram , Xu Yuexin , Warren Edus H. , Tykodi Scott S. , Tretiakova Maria
Published: February 2023

5T4 (trophoblast glycoprotein encoded by TPBG) is a cancer/testis antigen highly expressed in renal cell carcinoma (RCC) and many other cancers but rarely in normal tissues. Interest in developing 5T4 as a prognostic biomarker and direct targeting of 5T4 by emerging receptor-engineered cellular immunotherapies has been hampered by the lack of validated 5T4-specific reagents for immunohistochemistry (IHC). We tested 4 commercially available monoclonal antibodies (mAbs) for the detection of 5T4 in formalin-fixed, paraffin-embedded RCC and normal tissues. Using parental and TPBG-edited A498 cells, 3 mAbs showed 5T4 specificity. Further analyses focused on 2 mAbs with the most robust staining (MBS1750093, Ab134162). IHC on tissue microarrays incorporating 263 renal tumors showed high staining concordance of these 2 mAbs ranging from 0.80 in chromophobe RCC to 0.89 in advanced clear cell RCC (ccRCC). MBS1750093, the most sensitive, exhibited 2+/3+ staining in papillary RCC (92.2%) > advanced ccRCC (60.0%) > chromophobe RCC (43.6%) > localized ccRCC (39.6%) > oncocytoma (22.7%). RNA in situ hybridization also revealed high levels of TPBG RNA were present most frequently in papillary and advanced ccRCC. In advanced ccRCC, there was a trend towards higher 5T4 expression and regional or distant metastases. Normal organ controls showed no or weak staining with the exception of focal moderate staining in kidney glomeruli and distal tubules by IHC. These data identify mAbs suitable for detecting 5T4 in formalin-fixed, paraffin-embedded tissues and demonstrate both interpatient and histologic subtype heterogeneity. Our validated 5T4 IHC protocol will facilitate biomarker studies and support the therapeutic targeting of 5T4.
The Intestinal Tract Brush Border in Young Children Uniformly Expresses Guanylate Cyclase C
Authors: Di Guglielmo Matthew D. , Holbrook Jennifer , Stabley Deborah , Robbins Katherine M. , Boyce Bobbie , Hardy Heather , Adeyemi Adebowale
Published: February 2023

The present study examined staining of guanylate cyclase C (GCC/GUCY2C) in the small and large intestines of children younger than age 7 years. Normal intestinal tissue from children aged 0 to 7 years was stained using GCC, uroguanylin, and villin antibodies and scored for staining intensity. A subset underwent quantitative real-time polymerase chain reaction. Data were analyzed using t test of independent means, descriptive statistics, and logistic regression. Four hundred sixty-four specimens underwent immunohistochemistry; 291 specimens underwent real-time polymerase chain reaction. GCC, villin, and uroguanylin were detected across age groups and anatomic sites. No significant differences were identifiable across age groups. GUCY2C and uroguanylin mRNA was detected in all samples, with no variability of statistical significance of either target-to-villin normalization between any age cohorts. A gradient of expression of GCC across age groups does not seem to exist.
Boston Febrile Infant Algorithm 2.0: Improving Care of the Febrile Infant 1–2 Months of Age
Authors: Dorney Kate , Neuman Mark I. , Harper Marvin B. , Bachur Richard G.
Published: February 2023

Introduction:

Significant variation exists in the management of febrile infants, particularly those between 1 and 2 months of age. An established algorithm for well-appearing febrile infants 1–2 months of age guided clinical care for three decades in our emergency department. With mounting evidence for procalcitonin (PCT) to detect invasive bacterial infection (IBI), we revised our algorithm intending to decrease lumbar punctures (LPs) and antibiotic administration without increasing hospitalizations, revisits, or missed IBI.

Methods:

The algorithm’s risk stratification was revised based on the expert review of evidence regarding test performance of PCT for IBI in febrile infants. With the revision, routine LP and empiric antibiotics were not recommended for low-risk infants. We used quality improvement strategies to disseminate the revised algorithm and reinforce uptake. The primary outcomes were the proportion of infants undergoing lumbar punctures or receiving antibiotics. Admission rates, 72-hour revisits requiring admission, and missed IBI were monitored as balancing measures.

Results:

We studied 616 infants including 326 (52.9%), after the implementation of the revised algorithm. LP was performed in 66.2% prerevision and 31.9% postrevision (34.3% absolute reduction, P < 0.001). Antibiotic administration decreased by 26.2% (pre 62.4% to post 36.2%, P < 0.001) and hospitalization rates decreased by 8.1% (P = 0.03). There have been no missed IBIs. Adherence to the pathway led to a sustained reduction in LPs and antibiotic administration for 24 months.

Conclusion:

A revised pathway with the addition of PCT resulted in a safe, sustained reduction in LPs and reduced antibiotic administration in febrile infants 1–2 months of age.
Implementation of a Standardized Premedication Bundle to Improve Procedure Success for Nonemergent Neonatal Intubations
Authors: Diego Ellen K. , Malloy Katherine , Cox Toby , Broomall Allison , Orr Laura , Baxter Christina , Meany Sarah , Baker Nicole , Fraser Jennifer , Corbin Kelly Sanders , Gregoski Mathew J. , Wagner Carol L. , Ross Julie R.
Published: February 2023

Introduction:

The American Academy of Pediatrics recommends premedication for all nonemergent neonatal intubations, yet there remains significant variation in this practice nationally. We aimed to standardize our unit’s premedication practices for improved intubation success and reduced adverse events.

Methods:

The study workgroup developed educational material and protocol content. Process measures included premedication use, education, and audit form completion. Primary (success on first intubation attempt and adverse event rates) and secondary (trainee success) study outcomes are displayed using statistical process control charts and pre-post cohort comparisons.

Results:

Forty-seven percent (97/206) of nurses completed educational intervention before protocol release, with an additional 20% (42/206) following a staff reminder. Two hundred sixteen (216) patients were intubated per protocol with 81% (174/216) audit completion. Compared with baseline (n = 158), intubation attempts decreased from 2 (IQR, 1–2) to 1 (IQR, 1–2) (P = 0.03), and success on the first attempt increased from 40% (63/158) to 57% (124/216) (P < 0.01), with a notable improvement in trainee success from less than 1% (1/40) to 43% (31/72) (P < 0.01). The rate of severe and rare adverse events remained stable; however, there was a rise in nonsevere events from 30% (48/158) to 45% (98/216). The tachycardia rate increased with atropine use. There was no change in chest wall rigidity, number of infants unable to extubate following surfactant, or decompensation awaiting medications.

Conclusions:

Standardizing procedural care delivery reduced intubation attempts and increased the attempt success rate. However, this was accompanied by an increase in the rate of nonsevere adverse events.
In Vivo Performance of a Machine Learning Model Predicting Pediatric Sepsis at Triage
Authors: Piroutek Mary Jane , Heyming Theodore W. , Knudsen-Robbins Chloe , Feaster William , Lee Kent , Ehwerhemuepha Louis
Published: February 2023

Introduction:

Sepsis is a leading cause of pediatric mortality across the globe. Early recognition reduces mortality; and improve outcomes however, rapid detection remains difficult. Although physiologic mechanisms contribute to the complexity the epidemiology of pediatric Emergency Department (ED) visits also contributes. A variety of sepsis screening methods have been designed, from alerts based on triage temperature and heart rate to more complex algorithms. Evaluation of such tools has suggested improved identification, yet there is a lack of definitive data.

Objective:

The objective of this study was to evaluate the implementation and performance of the S2T2 (Sepsis Screening Triage Tool) in a pediatric ED.

Methods:

The S2T2 is a multiclass stochastic gradient boosting machine learning model recently developed at the study institution. It uses ED triage data and historical data mined from electronic health record to predict sepsis potential at triage. S2T2 was operationalized on 2/1/21; performance data for this study were collected over the first 7 months of implementation (to 8/31/21). Sensitivity and specificity were assessed by comparison with final International Classification of Disease-10 diagnoses codes. The pediatric ED at which this model was developed is a level-2 pediatric trauma center with an annual census of approximately 96,000.

Results:

In total, 43,337 patients were included, 41 with severe sepsis and 121 with sepsis. S2T2 demonstrated a sensitivity of 41.5% and specificity of 99.2% for severe sepsis, and a sensitivity of 25.6% and specificity of 99.2% for sepsis.

Conclusion:

S2T2 may aide in the identification of pediatric patients at risk for sepsis, potentially allowing for accelerated diagnosis, intervention, improved care, and better outcomes.
MMP9 as a Potential Biomarker in 631 Human Implant-Induced Fibrotic Capsules A Systematic Analysis and Biomarker Study
Authors: Kuehlmann Britta , Bonham Clark Andrew , Gurtner Geoffrey C. , Prantl Lukas
Published: February 2023

Background:

Capsular fibrosis (CF) often occurs around biomedical devices following implantation causing pain, discomfort, and device failure. Breast implantation remains among the most common medical procedures worldwide. Revealing specific genes that drive fibrotic deposition will help us to garner a better understanding of the pathophysiology of this disease and develop different strategies to combat it.

Methods:

Here, we collected 631 capsules around breast implants and were able to connect clinical baseline characteristics with histopathological findings. Additionally, we were able to conduct the first large systematic analysis to identify differentially-expressed genes in fibrotic human tissue samples, comparing the lowest form of fibrosis with the most aggravated one.

Results:

We identified 2,559 differentially-expressed genes upon which we performed a knowledge-based network generation and pathway association study to identify putative novel biomarkers for capsular fibrosis. We were able to show changes of cellular influx during progression of CF and distinguish several genes as potential clinical biomarkers and drug targets. Among these, MMP9 was one of the most upregulated (p-value: 0.006) and is attractive due to its wide detectability.

Conclusions:

MMP9 seems to be a potential biomarker to detect capsular fibrosis. It is a measurable indicator that can easily be detected in blood, sputum, and urine. For the diagnosis of fibrosis this biomarker might be exceedingly beneficial to developing novel screening methods and prophylaxes.

Clinical Relevance Statement:

Discovering biomarkers at the earliest and mildest stages for the diagnosis of fibrosis is clinically important. Our results bring new hope for biomarker-based diagnosis for CF.
Modified Surgical Model for Genito-Urinary Vascularized Composite Allotransplantations: An Anatomical Study
Authors: Ruiz François , Cetrulo Curtis L. , Timsit Marc-Olivier , Lantieri Laurent , Lellouch Alexandre G.
Published: February 2023

Total penile reconstruction represents a surgical challenge. Autologous reconstructions offer limited aesthetic results as well as variable urinary function recovery. To date, five Genito-Urinary Vascularized Composite Allotransplantations (GUVCA) have been performed worldwide. However, in all cases, vascular complications have been reported. The objective of this study is to develop a modified surgical model for penile allotransplantation to limit the number of microsurgical anastomoses while ensuring vascular reliability. We studied penile allotransplantation by performing dissections on 12 subjects. The study was carried out to ensure the vascularization of the entire penis shaft while limiting the number of anastomoses.

The penis vasculature includes numerous angiosomes between its different subunits. The penile skin envelope is supplied by both external and internal pudendal vessels. The cavernous and spongy bodies are supplied by terminal branches of the internal pudendal vessels. The anterior pubic osteotomy approach allows access to the root of the cavernous bodies and to the Alcock ducts. This modified surgical model for penile allotransplantation could help future teams involved in GUVCA to improve urinary and sexual function.
TQIP mortality reporting system case reports: Unanticipated mortality due to failures in clinical performance
Authors: Williams Regan F. , Davis Kimberly A. ,   the ACS TQIP Mortality Reporting System Writing Group
Published: February 2023

The Trauma Quality Improvement Program Mortality Reporting System is an online anonymous case reporting system designed to share experiences from rare events that may have contributed to unanticipated mortality at contributing trauma centers. The Trauma Quality Improvement Program Mortality Reporting System Working group monitors submitted cases and organizes them into emblematic themes. This report summarizes unanticipated mortality from two cases of failure of clinical performance and presents strategies to mitigate these events locally with the hope of decreasing unanticipated mortality nationwide.
Orthotopic Transplantation of the Full-length Porcine Intestine After Normothermic Machine Perfusion
Authors: Abraham Nader , Ludwig Elsa K. , Schaaf Cecilia R. , Veerasammy Brittany , Stewart Amy S. , McKinney Caroline , Freund John , Brassil John , Samy Kannan P. , Gao Qimeng , Kahan Riley , Niedzwiecki Donna , Cardona Diana M. , Garman Katherine S. , Barbas Andrew S. , Sudan Debra L. , Gonzalez Liara M.
Published: February 2023

Background.

Successful intestinal transplantation is currently hindered by graft injury that occurs during procurement and storage, which contributes to postoperative sepsis and allograft rejection. Improved graft preservation may expand transplantable graft numbers and enhance posttransplant outcomes. Superior transplant outcomes have recently been demonstrated in clinical trials using machine perfusion to preserve the liver. We hypothesized that machine perfusion preservation of intestinal allografts could be achieved and allow for transplantation in a porcine model.

Methods.

Using a translational porcine model, we developed a device for intestinal perfusion. Intestinal samples were collected at the time of organ procurement, and after 6 h of machine perfusion for gross and histologic evaluation, hourly chemistry panels were performed on the perfusate and were used for protocol optimization. Following transplantation, porcine recipient physical activity, systemic blood parameters, and vital signs were monitored for 2 d before sacrifice.

Results.

In initial protocol development (generation 1, n = 8 grafts), multiple metabolic, electrolyte, and acid-base derangements were measured. These factors coincided with graft and mesenteric edema and luminal hemorrhage and were addressed with the addition of dialysis. In the subsequent protocol (generation 2, n = 9 grafts), differential jejunum and ileum perfusion were observed resulting in gross evidence of ileal ischemia. Modifications in vasodilating medications enhanced ileal perfusion (generation 3, n = 4 grafts). We report successful transplantation of 2 porcine intestinal allografts after machine perfusion with postoperative clinical and gross evidence of normal gut function.

Conclusions.

This study reports development and optimization of machine perfusion preservation of small intestine and successful transplantation of intestinal allografts in a porcine model.
Pilot Study of the Effects of Paced Breathing on Measures of Convergent and Divergent Thinking
Authors: Wallace McKenzie B. , Costa Amy N. , Ferguson Bradley J. , Carey Megan A. , Rzeppa Chloe , Kille Briana M. , Drysdale David R. , Sutton Briann E. , Shuler Brianne H. , Johnson Ryan P. , Kwenda Elizabeth P. , Hadley Jamie , Snyders Whitney , Beversdorf David Q.
Published: February 2023

Background:

The ability of the autonomic nervous system’s stress response to impair aspects of cognitive flexibility is known. However, the ability to modulate the sympathetic response and improve these cognitive impairments via nonpharmacological intervention, such as paced breathing (PB), requires further investigation.

Objective:

To better elucidate the effects of PB on cognition.

Method:

We employed a PB protocol in a total of 52 healthy men and women and measured performance on convergent and divergent cognitive tasks, perceived stress, and physiological measures (eg, blood pressure, heart rate). Participants attended two experimental sessions consisting of either PB or normal breathing followed by cognitive assessments including convergent (compound remote associate, anagram) and divergent (alternate use, fluency) tasks. Experiment 2 consisted of more difficult versions of cognitive tasks compared with Experiment 1.

Results:

In Experiment 1, PB significantly reduced the female participants’ systolic and diastolic blood pressure immediately after the breathing protocol without affecting their cognition. In Experiment 2, PB significantly reduced perceived stress immediately after the breathing protocol, regardless of sex. There was no effect on cognition in Experiment 2, but a correlation was observed between perceived stress change and anagram number solved change.

Conclusion:

While PB modulates sympathetic activity in females, there was a lack of improvement in cognitive flexibility performance. At least for a single trial of PB, cognitive flexibility did not improve.
Learning Curve for Transanal Total Mesorectal Excision for Low Rectal Malignancy
Authors: Matsuda Takeru , Ryuichiro Sawada , Hasegawa Hiroshi , Yamashita Kimihiro , Harada Hitoshi , Urakawa Naoki , Goto Hironobu , Kanaji Shingo , Oshikiri Taro , Kakeji Yoshihiro
Published: February 2023

Background:

Although transanal total mesorectal excision (TaTME) is a promising treatment for low rectal cancers; it is considered technically demanding, and the number of cases required to become proficient in TaTME remains unknown. The purpose of this study was to assess the TaTME learning curve based on the TME completion time.

Study Design:

This retrospective analysis comprised of 128 individuals who received TaTME between September 2016 and December 2021. The cumulative sum method was used to generate the learning curve. The duration of the procedure from the beginning to the end of the circumferential rendezvous was used to define the TME completion time.

Results:

The learning curve consists of three phases: phase I (learning phase: cases 1–38), phase II (consolidation phase: cases 39–70), and phase III (maturing phase: cases 71–128). As the phases varied, both the overall operative time and TME completion time considerably decreased. Through the three phases of TaTME, intraoperative adverse events decreased, and in phase III, none occurred. Only one instance of local recurrence occurred during phase III, while none occurred during phase I or II.

Conclusion:

After 70 operations, the surgeon could join the mastery phase of TaTME based on the TME completion time. After the mastering phase began, there were no intraoperative negative occurrences. From the beginning, the oncological safety could be guaranteed.
Does CPT Modifier 22 Appropriately Reflect a Difficult Pancreaticoduodenectomy? Retrospective Analysis of Operative Outcomes and Cost
Authors: Mustansir Fatima , Jajja Mohammad Raheel , Lovasik Brendan P , Sharma Jyotirmay , Lin Edward , Sweeney John F , Sarmiento Juan M
Published: February 2023

BACKGROUND:

CPT coding allows addition of a 2-digit modifier code to denote particularly difficult procedures necessitating additional reimbursement, called the modifier 22. The use of modifier 22 in relation to pancreatic surgery and outcomes, specifically pancreaticoduodenectomy (PD), has not been explored.

STUDY DESIGN:

All PDs performed from 2010 to 2019 at a quaternary healthcare system were analyzed for differences in preoperative characteristics, outcomes, and cost based on the use of modifier 22. Adjusted logistic regression analysis was used to identify factors predictive of modifier 22 use.

RESULTS:

A total of 1,284 patients underwent PD between 2010 and 2019; 1,173 with complete data were included, of which 320 (27.3%) were coded with modifier 22. Patients coded with modifier 22 demonstrated a significantly longer duration of surgery (365.9 ± 168.4 vs 227 ± 97.1; p < 0.001). They also incurred significantly higher cost of index admission ($37,446 ± 34,187 vs $28,279 ± 27,980; p = 0.002). An adjusted multivariable analysis (specifically adjusted for surgeon variation) revealed duration of surgery (p < 0.001), neoadjuvant chemotherapy (p = 0.039), class II obesity (p = 0.019), and chronic pancreatitis (p = 0.005) to be predictive of modifier 22 use.

CONCLUSIONS:

Despite the subjective nature of this CPT modifier, modifier 22 is an appropriate marker of intraoperative difficulty. Preoperative and intraoperative characteristics that lead to its addition may be used to further delineate difficult PDs.
Shiga toxin-producing Escherichia coli (STEC) and atypical enteropathogenic E. coli (aEPEC) in Swedish retail wheat flour
Authors: Soderlund Robert , Flink Catarina , Aspán Anna , Eriksson Erik
Published: February 2023

Wheat flour has been identified as the source of multiple outbreaks of gastrointestinal disease caused by shiga-toxin producing Escherichia coli (STEC). We have investigated the presence and genomic characteristics of STEC and related atypical enteropathogenic E. coli (aEPEC) in 200 bags of Swedish-produced retail wheat flour, representing 87 products and 25 brands. Samples were enriched in modified TSB and screened with real-time PCR targeting stx1, stx2, eae, and the serogroups O157, O121, and O26. Isolation was performed by IMS for suspected STEC/aEPEC O157, O121 and O26, and by screening pools of colonies for other STEC. Real-time PCR after enrichment revealed 12% of samples to be positive for shiga toxin genes (stx1 and/or stx2) and 11% to be positive for intimin (eae). Organic production, small-scale production or whole grain did not significantly influence shiga toxin gene presence or absence in a generalized linear mixed model analysis. Eight isolates of STEC were recovered, all of which were intimin negative. Multiple serotype/sequence type/shiga-toxin subtype combinations were recovered which have also been found in flour samples in other European countries. Most STEC types recovered were associated with sporadic cases of STEC among humans in Sweden, but no types known to have caused outbreaks or severe cases of disease (i.e. haemolytic-uraemic syndrome) were found. The most common finding was O187:H28 ST200 with stx2g, with possible links to cervid hosts. Wildlife associated with crop damage is a plausible explanation for at least some of the surprisingly high frequency of STEC in wheat flour.
Haemophilus Influenzae bloodstream infection and third-generation cephalosporins susceptibility testing: a comparative case study using EUCAST and CLSI guidelines
Authors: Merlino John , Rizzo Sophia , English Suzanne , Baskar Sai Rupa , Siarakas Steven , Mckew Genevieve , Fernanado Shelanah , Gray Timothy
Published: February 2023

Introduction. In this comparative case study, we discuss clinically-relevant discrepancies of antimicrobial susceptibility testing (AST) interpretation for ceftriaxone against a non-typable, beta-lactamase negative, ampicillin-resistant (BLNAR) Haemophilus influenzaeisolated from a blood culture.
Case report: A 74 year old man presented with a 3-day illness characterised by shortness of breath and dry cough, and was noted to be febrile and hypoxic on admission. A blood culture bottle flagged positive with Gram-negative coccobacilli, later identified as Haemophilus influenzae with the patient commenced on ceftriaxone. The isolate was beta-lactamase negative and antibiotic susceptibility testing (AST) using disc diffusion revealed the isolate resistant to ceftriaxone and ampicillin by EUCAST methodology, with the patient subsequently changed to amoxicillin/clavulanate. Further AST using the CLSI methodology in parallel demonstrated discrepant results between the two susceptibility methods. The patient recovered without complications.
Conclusion. This discrepancy could lead to inconsistent reporting of susceptibilities between laboratories, and consequently antibiotic prescribing, especially for invasive isolates. As more laboratories adopt EUCAST methodologies for AST interpretation in Australia and globally, it is important for clinicians to consider the clinical implications of these methodological discrepancies.
Acidaminococcus homini s sp. nov., Amedibacillus hominis sp. nov., Lientehia hominis gen. nov. sp. nov., Merdimmobilis hominis gen. nov. sp. nov., and Paraeggerthella hominis sp. nov., isolated from human faeces
Authors: Abdugheni Rashidin , Li Dan-Hua , Wang Yu-Jing , Du Meng-Xuan , Zhou Nan , Liu Chang , Liu Shuang-Jiang
Published: February 2023

The human gastrointestinal tract is inhabited by various microorganisms, including thousands of bacterial taxa that have yet to be cultured and characterized. In this report, we describe the isolation, cultivation, genotypic and phenotypic characterization and taxonomy of five novel anaerobic bacterial strains that were recovered during the massive cultivation and isolation of gut microbes from human faecal samples. On the basis of the polyphasic taxonomic results, we propose two novel genera and five novel species. They areAcidaminococcus hominissp. nov. (type strain NSJ-142T=CGMCC 1.17903T=KCTC 25346T),Amedibacillus hominissp. nov. (type strain NSJ-176T=CGMCC 1.17933T=KCTC 25355T),Lientehia hominisgen. nov. sp. nov. (type strain NSJ-141T=CGMCC 1.17902T=KCTC 25345T),Merdimmobilis hominisgen. nov. sp. nov. (type strain NSJ-153T=CGMCC 1.17915T=KCTC 25350T) andParaeggerthella hominissp. nov. (type strain NSJ-152T=CGMCC 1.17914T=KCTC 25349T).
Near infrared conjugated polymer nanoparticles (CPN™) for tracking cells using fluorescence and optoacoustic imaging
Authors: Muñiz-García Ana , Pichardo Alejandra Hernandez , Littlewood James , Sharkey Jack , Wilm Bettina , Peace Hannah , O’Callaghan Dermott , Green Mark , Taylor Arthur , Murray Patricia
Published: February 2023

Tracking the biodistribution of cell therapies is crucial for understanding their safety and efficacy. Optical imaging techniques are particularly useful for tracking cells due to their clinical translatability and potential for intra-operative use to validate cell delivery. However, there is a lack of appropriate optical probes for cell tracking. The only FDA-approved material for clinical use is indocyanine green (ICG). ICG can be used for both fluorescence and photoacoustic imaging, but is prone to photodegradation, and at higher concentrations, undergoes quenching and can adversely affect cell health. We have developed novel near-infrared imaging probes comprising conjugated polymer nanoparticles (CPNs™) that can be fine-tuned to absorb and emit light at specific wavelengths. To compare the performance of the CPNs™ with ICG forin vivocell tracking, labelled mesenchymal stromal cells (MSCs) were injected subcutaneously in mice and detected using fluorescence imaging (FI) and a form of photoacoustic imaging called multispectral optoacoustic tomography (MSOT). MSCs labelled with either ICG or CPN™ 770 could be detected with FI, but only CPN™ 770-labelled MSCs could be detected with MSOT. These results show that CPNs™ show great promise for tracking cellsin vivousing optical imaging techniques, and for some applications, out-perform ICG.
Food Insecurity amid COVID-19 Lockdowns: Assessing Sociodemographic Indicators of Vulnerability in Harar and Kersa, Ethiopia
Authors: Muir Jonathan A. , Dheresa Merga , Madewell Zachary J. , Getachew Tamirat , Mengesha Gezahegn , Whitney Cynthia G. , Assefa Nega , Cunningham Solveig A.
Published: February 2023

Objective

The COVID-19 pandemic was associated with widespread social disruptions, as governments implemented lockdowns to quell disease spread. To advance knowledge of consequences for households in lower-income countries, we examine food insecurity during the pandemic period.

Design

Cross-sectional study using logistic regression to examine factors associated with food insecurity. Data were collected between August and September of 2021 through a Health and Demographic Surveillance System (HDSS) using a survey instrument focused on knowledge regarding the spread of COVID-19; food availability; COVID-19 related shocks/coping; under-five child healthcare services; and healthcare services for pregnant women.

Setting

The study is set in two communities in Eastern Ethiopia, one rural and one urban.

Participants

A random sample of 880 households residing in Kersa and Harar.

Results

Roughly 16% of households reported not having enough food to eat during the pandemic, an increase of 6% since before the pandemic. After adjusting for other variables, households were more likely to report food insecurity if they were living in an urban area, were a larger household, had a family member lose employment, reported an increase in food prices, or were food insecure before the pandemic. Households were less likely to report food insecurity if they were wealthier or had higher household income.DiscussionAfter taking other characteristics into consideration, households in urban areas were at higher risk for food insecurity. These findings point to the need for expanding food assistance programs to more urban areas to help mitigate the impact of lockdowns on more vulnerable households.
A Prospective Study Measuring Resident/Faculty Contour Concordance: A Potential Tool for Quantitative Assessment of Residents’ Performance in Contouring and Target Delineation
Authors: Nissen Caleb , Ying Jun , Kalantari Faraz , Patel Mausam , Prabhu Arpan V. , Kesaria Anam , Kim Thomas , Maraboyina Sanjay , Harrell Leslie , Xia Fen , Lewis Gary D.
Published: February 2023

Purpose/Objective(s)

Accurate target delineation/contouring is essential for radiation treatment planning and radiotherapy efficacy. As a result, improving the quality of target delineation is an important goal in the education of radiation oncology residents. The purpose of this study was to track the concordance of radiation oncology residents’ contours with faculty physicians’ contours over the course of one year to assess for patterns.

Materials/Methods

Residents in PGY levels of 2-4 were asked to contour target volumes which were compared to the finalized, faculty physician-approved contours. Concordance between resident and faculty physician contours was determined by calculating the Jaccard Concordance Index (JCI), ranging from 0 or no agreement to 1 or complete agreement. Mutivariate mixed effect models were used to assess the association of JCI to the fixed effect of PGY level and its interactions with cancer type and other baseline characteristics. Post hoc means of JCI were compared between PGY levels after accounting for multiple comparisons using a Tukey’s method.

Results

In total, 958 structures from 314 patients collected during the 2020-2021 academic year were studied. The mean JCI was 0.77, 0.75, and 0.61 for the levels of PGY-4, PGY-3, and PGY-2, respectively. JCI score in PGY-2 was found lower than those of PGY-3 and PGY-4 respectively (P’s<0.001). No statistically significant difference of JCI score was found when comparing between PGY-3 and PGY-4 levels. The average JCI score was lowest (0.51) for primary head/neck cancers and highest (0.80) for gynecologic cancers.

Conclusion

Tracking and comparing the concordance of resident contours and faculty physician contours is an intriguing method of assessing resident performance in contouring and target delineation and could potentially serve as a quantitative metric in radiation oncology resident evaluation, which is lacking currently. However, additional study is necessary before this technique can be incorporated into residency assessments.
Prediction of Gastrointestinal Bleeding Hospitalization in Hemodialysis
Authors: Larkin John W. , Lama Suman , Chaudhuri Sheetal , Willetts Joanna , Winter Anke C. , Jiao Yue , Stauss-Grabo Manuela , Usvyat Len A. , Hymes Jeffrey L. , Maddux Franklin W. , Wheeler David C. , Stenvinkel Peter , Floege Jürgen
Published: February 2023

Gastrointestinal bleeding (GIB) is a clinical challenge in kidney failure. The INSPIRE group assessed if machine learning could assist with determining a hemodialysis (HD) patient’s 180-day GIB hospitalization risk. Model was developed using adult HD patient data from United States (2017-2020). Patient data was randomly split (50% training, 30% validation, and 20% testing). HD treatments ≤ 180 days before GIB hospitalization were classified as positive observations, and others were negative observations. Datasets were randomly sampled to build an XGBoost model that considered 386 exposures initially and was refined to the top 50 exposures. Unseen testing dataset was used to determine final model performance. Incidence of 180-day GIB hospitalization was 1.18% in the HD population (n=451,579), and 1.16% among patients in the testing dataset (n=27,991). Model showed an area under the curve=0.69, sensitivity=57.9%, specificity=68.9%, accuracy=68.8% and balanced accuracy=63.4%. Exposures with largest effect size per Shapley values were older age (group mean GIB event=68.2 years vs no GIB event=63.4 years), shorter days since last all-cause hospital admission (group mean GIB event=203.2 days vs no GIB event=253.2 days), and higher serum 25-hydroxy (OH) vitamin D levels from most recent lab (group mean GIB event=33.4 ng/mL vs no GIB event=30.5 ng/mL). Other important predictors included lower hemoglobin and iron indices, longer dialysis vintage, and proton pump inhibitor use. Model appears suitable for early detection of GIB event risk in HD, yet prospective testing is needed. The association between higher 25OH vitamin D and GIB events was unexpected and warrants investigation.
X-Chromosome Association Study in Latin American Cohorts Identifies New Loci in Parkinson Disease
Authors: Leal Thiago P , French-Kwawu Jennifer N , Gouveia Mateus H , Borda Victor , Inca-Martinez Miguel , Mason Emily A , Horimoto Andrea RVR , Loesch Douglas P , Sarihan Elif I , Cornejo-Olivas Mario R , Torres Luis E , Mazzetti-Soler Pilar E , Cosentino Carlos , Sarapura-Castro Elison H , Rivera-Valdivia Andrea , Medina Angel C , Dieguez Elena M , Raggio Víctor E , Lescano Andrés , Tumas Vitor , Borges Vanderci , Ferraz Henrique B , Rieder Carlos R , Schumacher-Schuh Artur , Santos-Lobato Bruno L , Velez-Pardo Carlos , Jimenez-Del-Rio Marlene , Lopera Francisco , Moreno Sonia , Chana-Cuevas Pedro , Fernandez William , Arboleda Gonzalo , Arboleda Humberto , Arboleda Bustos Carlos E , Yearout Dora , Lima-Costa Maria F , Tarazona Eduardo , Zabetian Cyrus , Thornton Timothy A , O’Connor Timothy D , Mata Ignacio F
Published: February 2023

Sex differences in Parkinson Disease (PD) risk are well-known. However, it is still unclear the role of sex chromosomes in the development and progression of PD. We performed the first X-chromosome Wide Association Study (XWAS) for PD risk in Latin American individuals. We used data from three admixed cohorts: (i) Latin American Research consortium on the GEnetics of Parkinson’s Disease (n=1,504) as discover cohort and (ii) Latino cohort from International Parkinson Disease Genomics Consortium (n = 155) and (iii) Bambui Aging cohort (n= 1,442) as replication cohorts. After developing a X-chromosome framework specifically designed for admixed populations, we identified eight linkage disequilibrium regions associated with PD. We fully replicated one of these regions (top variant rs525496; discovery OR [95%CI]: 0.60 [0.478 - 0.77], p = 3.13 ×10-5; replication OR: 0.60 [0.37-0.98], p = 0.04). rs525496 is an expression quantitative trait loci for several genes expressed in brain tissues, includingRAB9B, H2BFM, TSMB15BandGLRA4. We also replicated a previous XWAS finding (rs28602900), showing that this variant is associated with PD in non-European populations. Our results reinforce the importance of including X-chromosome and diverse populations in genetic studies.
Design and feasibility of an Alzheimer’s disease blood test study in a diverse community-based population
Authors: Li Melody , Li Yan , Schindler Suzanne E. , Yen Daniel , Sutcliffe Siobhan , Babulal Ganesh M. , Benzinger Tammie L.S. , Lenze Eric J. , Bateman Randall J.
Published: February 2023

INTRODUCTION

Alzheimer’s disease (AD) blood tests are likely to become increasingly important in clinical practice, but need to be evaluated in diverse groups before use in the general population.

METHODS

This study enrolled a community-based sample of older adults in the Saint Louis, Missouri, USA area. Participants completed a blood draw, AD8® dementia screening interview, Montreal Cognitive Assessment (MoCA), and survey about their perceptions of the blood test. A subset of participants completed additional blood collection, amyloid PET, MRI, and Clinical Dementia Rating® (CDR).

RESULTS

Of the 859 participants enrolled in this ongoing study, 20.6% self-identified as Black or African American. The AD8 and MoCA correlated moderately with the CDR. The blood test was well-accepted by the cohort, but perceived more positively by White and highly educated individuals.

DISCUSSION

Studying an AD blood test in a diverse population is feasible, and may accelerate accurate diagnosis and implementation of effective treatments.
Immunogenicity of the BA.1 and BA.4/BA.5 SARS-CoV-2 Bivalent Boosts: Preliminary Results from the COVAIL Randomized Clinical Trial
Authors: Branche Angela R. , Rouphael Nadine G. , Losada Cecilia , Baden Lindsey R. , Anderson Evan J. , Luetkemeyer Anne F. , Diemert David J. , Winokur Patricia L. , Presti Rachel M. , Kottkamp Angelica C. , Falsey Ann R. , Frey Sharon E. , Rupp Richard , Bäcker Martín , Novak Richard M. , Walter Emmanuel B. , Jackson Lisa A. , Little Susan J. , Immergluck Lilly C. , Mahgoub Siham M. , Whitaker Jennifer A. , Babu Tara M. , Goepfert Paul A. , Fusco Dahlene N. , Atmar Robert L. , Posavad Christine M. , Netzl Antonia , Smith Derek J. , Telu Kalyani , Mu Jinjian , Makowski Mat , Makhene Mamodikoe K. , Crandon Sonja , Montefiori David C. , Roberts Paul C. , Beigel John H.
Published: February 2023

In a randomized clinical trial, we compare early neutralizing antibody responses after boosting with bivalent SARS-CoV-2 mRNA vaccines based on either BA.1 or BA.4/BA.5 Omicron spike protein combined with wildtype spike. Responses against SARS-CoV-2 variants exhibited the greatest reduction in titers against currently circulating Omicron subvariants for both bivalent vaccines.
Cross-ancestry genetic architecture and prediction for cholesterol traits
Authors: Momin Md. Moksedul , Zhou Xuan , Hyppönen Elina , Benyamin Beben , Lee S. Hong
Published: February 2023

While cholesterol is essential for human life, a high level of cholesterol is closely linked with the risk of cardiovascular diseases. Genome-wide association studies (GWASs) have been successful to identify genetic variants associated with cholesterol, which have been conducted mostly in white European populations. Consequently, it remains mostly unknown how genetic effects on cholesterol vary across ancestries. Here, we estimate cross-ancestry genetic correlation to address questions on how genetic effects are shared across ancestries for cholesterol. We find significant genetic heterogeneity between ancestries for total- and LDL-cholesterol. Furthermore, we show that single nucleotide polymorphisms (SNPs), which have concordant effects across ancestries for cholesterol, are more frequently found in the regulatory region, compared to the other genomic regions. Indeed, the positive genetic covariance between ancestries is mostly driven by the effects of the concordant SNPs, whereas the genetic heterogeneity is attributed to the discordant SNPs. We also show that the predictive ability of the concordant SNPs is significantly higher than the discordant SNPs in the cross-ancestry polygenic prediction. The list of concordant SNPs for cholesterol is available in GWAS Catalog (https://www.ebi.ac.uk/gwas/; details are in web resources section). These findings have relevance for the understanding of shared genetic architecture across ancestries, contributing to the development of clinical strategies for polygenic prediction of cholesterol in cross-ancestral settings
BioDecoder: A miRNA Bio-interpretable Neural Network Model for Noninvasive Diagnosis of Breast Cancer
Authors: Liu Lei , Lin Weili , Cao Suqi , Yang Liu , Gao Sheng , Jiao Na , Zhu Lixin , Zhu Ruixin , Wu Dingfeng
Published: February 2023

Early diagnosis of breast cancer remains a major clinical challenge. Liquid biopsy has become a powerful tool for cancer diagnosis by the aid of various the state-of-the-art detection technologies and artificial intelligence (AI) methods. Although the prediction performance is superior, the clinical application of existing AI models is greatly limited due to their poor interpretability. Here, we designed a miRNA-Gene-Module-Pathway-Disease biological decoding path, and developed BioDecoder thereof, a miRNA bio-interpretable neural network model for breast cancer early diagnosis. We demonstrated that BioDecoder could achieve early non-invasive diagnosis of breast cancer with a remarkable performance (AUC = 0.989) and showed strong generalizability in an external cohort (AUC = 0.890). Meanwhile, the biologically interpretable results of BioDecoder revealed that significant changes in metabolic pathway and oxidative phosphorylation were the main action pathways of circulating miRNA in breast cancer. Our study indicates that BioDecoder offers the promise of non-invasive early diagnosis of breast cancer and can be generalized to other cancers and corresponding biomarkers.