bluuebunny/crossref_metadata_2025 huggingface dataset:
Longitudinal Care Patterns and Utilization Among Patients With New-Onset Neck Pain by Initial Provider Specialty
Authors: Fenton Joshua J. , Fang Shao-You , Ray Monika , Kennedy John , Padilla Katrine , Amundson Russell , Elton David , Haldeman Scott , Lisi Anthony J. , Sico Jason , Wayne Peter M. , Romano Patrick S.
Published: August 2023

Study Design:

Retrospective cohort study.

Objective:

To compare utilization patterns for patients with new-onset neck pain by initial provider specialty.

Summary of Background Data:

Initial provider specialty has been associated with distinct care patterns among patients with acute back pain; little is known about care patterns among patients with acute neck pain.

Methods:

De-identified administrative claims and electronic health record data were derived from the Optum Labs Data Warehouse, which contains longitudinal health information on over 200M enrollees and patients representing a mixture of ages and geographical regions across the United States. Patients had outpatient visits for new-onset neck pain from October 1, 2016 to September 30, 2019, classified by initial provider specialty. Utilization was assessed during a 180-day follow-up period, including subsequent neck pain visits, diagnostic imaging, and therapeutic interventions.

Results:

The cohort included 770,326 patients with new-onset neck pain visits. The most common initial provider specialty was chiropractor (45.2%), followed by primary care (33.4%). Initial provider specialty was strongly associated with the receipt of subsequent neck pain visits with the same provider specialty. Rates and types of diagnostic imaging and therapeutic interventions during follow-up also varied widely by initial provider specialty. While uncommon after initial visits with chiropractors (≤2%), CT, or MRI scans occurred in over 30% of patients with initial visits with emergency physicians, orthopedists, or neurologists. Similarly, 6.8% and 3.4% of patients initially seen by orthopedists received therapeutic injections and major surgery, respectively, compared with 0.4% and 0.1% of patients initially seen by a chiropractor.

Conclusion:

Within a large national cohort, chiropractors were the initial provider for a plurality of patients with new-onset neck pain. Compared with patients initially seen by physician providers, patients treated initially by chiropractors or therapists received fewer and less costly imaging services and were less likely to receive invasive therapeutic interventions during follow-up.

Level of Evidence:

3.
Follicular Unit Excision in Patients of African Descent: A Skin-Responsive Technique
Authors: Umar Sanusi , Khanna Raveena , Lohlun Boudin , Maldonado Juan Carlos , Zollinger Maria , Osei-Tutu Achiamah , Gonzales Alejandro , Chouhan Kavish , Nusbaum Aron
Published: August 2023

BACKGROUND

Follicular unit excision is a favored minimally invasive hair transplantation method. However, it is suboptimal for many patients of African descent because of wide variations in hair and skin characteristics.

OBJECTIVE

To evaluate the performance of a skin-responsive follicular unit excision device, which accommodates hair curliness, skin thickness, and firmness in patients of African descent.

MATERIALS AND METHODS

The authors retrospectively evaluated patients who underwent scalp follicular unit (FU) excision using a skin-responsive technique at 7 multinational clinics. The preoperative donor grading for the anticipated difficulty used a scale with Class V indicating the highest degree of hair curliness, skin thickness, and firmness.

RESULTS

Of 64 eligible patients (45 males and 19 females), 28 had Class V FU excision donor grades. The mean transection rate for all patients was 3%–6%, which was highest in class V patients. Skin thickness and firmness had a greater effect on the maximum transection rate than hair curliness. Only 19 or 18 G punches were used.

CONCLUSION

The authors report consistence success of a new skin-responsive FU excision device for all patients of African descent with a mean graft transection rate of less than 10%. The findings support skin thickness and firmness as major influencers of graft attrition rate.
The Discovery of Radiocesium-bearing Microparticles Directly Delivered to a Person in Tokyo as a Result of the Fukushima Daiichi Nuclear Disaster
Authors: Higaki Shogo
Published: August 2023

The plume from Fukushima Dai-ichi Nuclear Power Plant (FDNPP) Unit 2, which reached the Tokyo metropolitan area on 15 March 2011 immediately after the FDNPP disaster, contained insoluble radiocesium-bearing microparticles (CsMPs). This study aimed to reanalyze a mask worn during the disaster to determine the ratio of CsMPs to radiocesium that directly arrived in the Tokyo metropolitan area as a plume immediately after the disaster. CsMPs were isolated from the non-woven masks worn at the Hongo Campus of the University of Tokyo from 15–16 March 2011 that trapped radioactive material from the accident. Twenty-two CsMPs with diameters in the range of 1.9–3.6 μm were found in the mask worn outdoors by one person. The CsMP radioactive ratio to overall radiocesium content of the mask was 9.9%. The CsMPs were collected more efficiently by the mask than by a suspended particulate matter filter. A face mask might trap CsMPs in a plume more efficiently than a suspended particulate matter filter. Determining the amount of CsMPs led to a reassessment of the internal dose by CsMPs that were inhaled by the public immediately after the FDNPP accident.
Alternative career paths for ophthalmologists
Authors: Callaway Natalia F. , Cunningham Emmett T.
Published: August 2023

Purpose

Traditionally, ophthalmologists complete training and then choose a clinical care setting. The skills required to become an ophthalmologist can be applied to a variety of alternative career paths within and beyond healthcare. Not unexpectedly, therefore, there is a growing trend for ophthalmologists to explore alternative career paths in both healthcare and the life science industry more broadly. In this invited editorial, we summarize the more commonly considered ‘alternative career paths,’ and provide personal perspectives that have helped us and others when weighing such options.

Recent findings

Prior to pursuing an alternative career path, it is important to reflect on one's motivations and goals. A number of alternative careers paths are available, and the choice of when and what to pursue is both personal and personalizable. While it can be difficult to know a priori whether and to what extent a given path will be both enjoyable and rewarding, insights and advice from those who have walked that path before you can be invaluable. We review the more common paths of administrative leadership, entrepreneurship and innovation, product development, healthcare policy, nonprofit organizations, and investing, noting that these are just examples of the many options currently available.

Ophthalmologists should feel empowered to design a career that is both purposeful and personally meaningful, as this will result ultimately in the greatest happiness and fulfillment. There is a world of opportunity available to those who are willing to explore and create their own path.
Anatomical resection improve relapse-free survival in colorectal liver metastases patients with KRAS/NRAS/BRAF mutation or right-sided colon cancer: a retrospective cohort study
Authors: Chang Wenju , Chen Yijiao , Zhou Shizhao , Ren Li , Xu Yuqiu , Zhu Dexiang , Tang Wentao , Ye Qinghai , Wang Xiaoying , Fan Jia , Wei Ye , Xu Jianmin
Published: August 2023

Background:

The type of liver resection (anatomical resection, AR or nonanatomical resection, NAR) for colorectal liver metastases (CRLM) is subject to debate. The debate may persist because some prognostic factors, associated with aggressive tumor biological behavior, have been overlooked.

Objective:

Our study aimed to investigate the characteristics of patients who would benefit more from anatomical resection for CRLM.

Methods:

729 patients who underwent hepatic resection of CRLM were retrospectively collected from June 2012 and May 2019. Treatment effects between AR and NAR were compared in full subgroup analyses. Tumor relapse-free survival (RFS) was evaluated by a stratified log-rank test and summarized with the use of Kaplan-Meier and Cox proportional hazards methods.

Results:

Among 729 patients, 235 (32.2%) underwent AR and 494 (67.8%) underwent NAR, we showed the favorable trends in RFS for AR compared with NAR in the patients with KRAS/NRAS/BRAF mutation (interaction P <0.001) or right-sidedness (interaction P <0.05). Patients who underwent AR had a markedly improved RFS compared with NAR, in the cohorts of RAS/NRAS/BRAF mutation (median RFS 23.2 VS 11.1 months, P <0.001) or right-sidedness (median RFS 31.6 VS 11.5 months, P <0.001); upon the multivariable analyses, AR (gene mutation: hazard ratio [HR] =0.506, 95% CI = 0.371-0.690, P <0.001; right-sidedness: HR =0.426, 95% CI =0.261-0.695, P =0.001) remained prognostic independently. In contrast, patients who underwent AR had a similar RFS compared with those who underwent NAR, in the cohorts of patients with gene wild-type tumors (median RFS 20.5 VS 21.6 months, P =0.333). or left-sidedness (median RFS 15.8 VS 19.5 months, P =0.294).

Conclusions:

CRLM patients with gene mutation or right-sidedness can benefit more from AR rather than from NAR.
Perioperative ketamine administration to prevent delirium and neurocognitive disorders after surgery: a systematic review and meta-analysis
Authors: Souad Fellous , Dubost Baptiste , Cambriel Amélie , Bonnet Marie-Pierre , Verdonk Franck
Published: August 2023

Background:

Surgery induces high rates of cognitive disorders, persisting for up to 12 months in elderly adults. This review aimed to assess the currently debated preventive effect of perioperative ketamine on postoperative delirium and postoperative neurocognitive disorders (POND).

Materials and Methods:

Systematic review and meta-analysis including all RCTs investigating the effects of perioperative ketamine administration in adult patients compared to placebo or no intervention on postoperative delirium and/or POND between January 2007 and April 2022. Database searches were conducted in PubMed Medline, Embase, Scopus, Central. Random effects models were used to pool overall estimates. The GRADE approach was used to assess the quality of evidence.

Results:

From 1379 records screened, 14 RCTs with 1618 patients randomized met our inclusion criteria with a high level of consensus among reviewers, amongst whom 50% were at low-moderate risk of bias. There was no between-group difference in postoperative delirium (8 trials, 1265 patients, OR 0.93, 95%CI [0.51; 1.70], I2=28%) and POND (5 trials, 494 patients, OR 0.52, 95%CI [0.15; 1.80]; I2=78%). There was no significant between-group difference in postoperative psychological adverse effects, level of pain, hospital length of stay, or mortality. Between-group subgroup analyses showed no difference in delirium or POND incidence according to surgical setting, ketamine dose, mode of administration, combination or not with other drug(s), and assessment timing or definition of cognitive disorders.

Conclusion:

Perioperative ketamine does not prevent postoperative delirium or POND. Significant study heterogeneity suggests that standardized measures for POND assessment and a specific focus on patients at high-risk for POND should be used to improve the comparability of future studies.
Identification and initial validation of maximal tumor area as a novel prognostic factor for overall and disease-free survival in patients with resectable colon cancer: a retrospective study
Authors: Ning Fei-Long , Gu Wan-Jie , Dai Lin-Zheng , Du Wan-Ying , Zeng Yong-Ji , Zhang Jia-Kui , Abe Masanobu , Liu Yan-Long , Zhang Rui , Zhang Chun-Dong
Published: August 2023

Background:

Tumor area may be a potential prognostic indicator. The present study aimed to determine and validate the prognostic value of tumor area in curable colon cancer.

Methods:

This retrospective study included a training and validation cohorts of patients who underwent radical surgery for colon cancer. Independent prognostic factors for overall survival (OS) and disease-free survival (DFS) were identified using Cox proportional hazards regression models. The prognostic discrimination was evaluated using the integrated area under the receiver operating characteristic curves (iAUCs) for prognostic factors and models. The prognostic discrimination between tumor area and other individual factors was compared, along with the prognostic discrimination between TNM staging system and other prognostic models. Two-sample Wilcoxon tests were carried out to identify significant differences between the two iAUCs. A two-sided P<0.05 was considered statistically significant.

Results:

A total of 3,051 colon cancer patients were included in the training cohort and 872 patients in the validation cohort. Tumor area, age, differentiation, T stage, and N stage were independent prognostic factors for both OS and DFS in the training cohort. Tumor area had a better OS and DFS prognostic discrimination characteristics than T stage, maximal tumor diameter, differentiation, tumor location, and number of retrieved lymph nodes. The novel prognostic model of T stage + N stage + tumor area (iAUC for OS, 0.714, P<0.001; iAUC for DFS, 0.694, P<0.001) showed a better prognostic discrimination than the TNM staging system (T stage + N stage; iAUC for OS, 0.664; iAUC for DFS, 0.658). Similar results were observed in an independent validation cohort.

Conclusions:

Tumor area was identified as an independent prognostic factor for both OS and DFS in curable colon cancer patients, and in cases with adequate number of retrieved lymph nodes. The novel prognostic model of combining T stage, N stage, and tumor area may be an alternative to the current TNM staging system.
Aspirin and lipoprotein(a) in primary prevention
Authors: Bhatia Harpreet S.
Published: August 2023

Purpose of review

Lipoprotein(a) [Lp(a)] is casually associated with cardiovascular diseases, and elevated levels are highly prevalent. However, there is a lack of available therapies to address Lp(a)-mediated risk. Though aspirin has progressively fallen out of favor for primary prevention, individuals with high Lp(a) may represent a high-risk group that derives a net benefit.

Recent findings

Aspirin has been demonstrated to have a clear benefit in secondary prevention of cardiovascular disease, but recent primary prevention trials have at best demonstrated a small benefit. However, individuals with elevated Lp(a) may be of high risk enough to benefit, particularly given interactions between Lp(a) and the fibrinolytic system / platelets, and the lack of available targeted medical therapies. In secondary analyses of the Women's Health Study (WHS) and the Aspirin in Reducing Events in the Elderly (ASPREE) trial, aspirin use was associated with a significant reduction in cardiovascular events in carriers of genetic polymorphisms associated with elevated Lp(a) levels. Further studies are needed, however, as these studies focused on narrower subsets of the overall population and genetic markers.

Individuals with elevated Lp(a) may benefit from aspirin therapy in primary prevention, but further study with plasma Lp(a) levels, broader populations, and randomization of aspirin are needed.
Refractory Burkitt Lymphoma With False-positive and False-negative Mass Detected on Positron Emission Tomography-computed Tomography After Chemotherapy
Authors: Shima Haruko , Takaki Torataro , Ito Jumpei , Iwabuchi Yu , Nakazawa Atsuko , Shimada Hiroyuki
Published: August 2023

A 4-year-old boy with an abdominal mass extending from the spleen to the lower umbilicus was diagnosed with Burkitt lymphoma stage III. Because the fluorodeoxyglucose uptake on positron emission tomography (PET)-computed tomography of the residual splenic tumor remained elevated, splenectomy was performed. The PET-positive area was composed of inflammatory infiltrates, whereas the PET-negative area was composed of a viable tumor surrounded by necrotic or dying tumor cells. The residual tumor may have been false-negative for PET because of its poor proliferative potential. In this case, the comparison of PET-computed tomography and pathologic findings demonstrates the simultaneous presence of a false-positive inflammatory lesion and a false-negative residual tumor.
Primitive Myxoid Mesenchymal Tumor of Infancy With Brain Metastasis Case Report and Literature Review
Authors: Raved Dan , Villani Anita , Hopyan Sevan , Chen Haiying , German Anna , Gupta Abha A.
Published: August 2023

Primitive myxoid mesenchymal tumor of infancy (PMMTI), a rare soft tissue tumor with distinct characteristics. PMMTI tends to have an aggressive local course, with multiple relapses and poor response to treatment. Rare cases of distant metastases have been described before. We described the second case of PMMTI with brain metastasis.
Evaluation of Intestinal Microbiota in Children With Sickle Cell Disease
Authors: Karahan Feryal , Yilmaz Serap Süzük , Bayrakdar Fatma , Tezol Özlem , Kuyucu Necdet , Kiliç Selçuk , Türkegün Merve , Ünal Selma
Published: August 2023

Background and Aims:

Sickle cell disease (SCD) is a chronic hemolytic anemia that may be life-threatening due to multisystemic effects. Identification of the factors which affect the pathophysiology of the disease is important in reducing mortality and morbidity. This study aimed to determine gut microbial diversity in children and adolescents with SCA compared with healthy volunteers and to evaluate the clinical impact of microbiota.

Materials and Methods:

The study included 34 children and young adolescents with SCD and 41 healthy volunteer participants. The microbiome was assessed by 16S rRNA sequencing in stool samples. Laboratory parameters of all participants, such as complete blood count and C-reactive protein values and clinical characteristics of SCD patients, were determined and compared, as well as clinical conditions of the patients, such as vascular occlusive crisis and/or acute chest syndrome, frequency of transfusions, intake of penicillin, hydroxyurea, and chelation therapy were recorded.

Results:

White blood cell count, hemoglobin, immature granulocyte and C-reactive protein levels were significantly higher in the patient group (P<0.05). Microbiota analysis revealed 3 different clusters among subjects; controls and 2 clusters in the SCD patients (patient G1 and G2 groups). Bacteroides spp. were more prevalent, while Dialester spp. and Prevotella spp. were less prevalent in SCD compared with controls (t=2.142, P<0.05). Patient G2 (n=9) had a higher prevalence of Bacteroides and a lower prevalence of Prevotella than patient G1 (n=25).

Conclusion:

In our study, there was a difference between SCD patients and the control group, while 2 different microbiota profiles were encountered in SCD patients. This difference between the microbiota of the patients was not found to affect the clinical picture (such as vascular occlusive crisis, acute chest syndrome).
Knowledge and Practice Behaviors Toward the Care of the Dying Among Chinese Oncology Nurses
Authors: Hou Xiaoting , Li Xin , Guo Renxiu , Wang Yun , He Shuangzhi , Yang Hong , Bai Dongli , Lu Yuhan
Published: August 2023

The quality of care provided to patients with cancer at the end of their lives remains unsatisfactory, especially during their last days and hours of life. This study aimed to investigate knowledge and practice behaviors of oncology nurses in relation to the care of the dying and to analyze the influencing factors. A convenience sample of 222 oncology nurses was recruited from 14 hospitals in Beijing, China, in January 2022. These nurses completed an online survey that included a demographic and work characteristics questionnaire and knowledge and practice behavior questionnaires regarding the care needs of dying cancer patients. The self-perceived knowledge and practice behavior of oncology nurses toward the care of the dying were found to be moderate. However, their understanding of airway management, restlessness, and delirium management was insufficient. In addition, their ability to effectively communicate recommendations for discontinuing unnecessary procedures, medications, treatments, and monitoring was inadequate. Nurses' previous end-of-life care education and experience of caring for dying patients influenced their knowledge. Nurses' practice settings, experience of caring for dying patients, and their knowledge were key factors in shaping their behaviors. Providing targeted continuing education for nurses in hospital settings and exploring the nursing pathway may be important ways to bridge their knowledge gap and enhance their practice behaviors toward caring for dying patients.
National Association of Medical Examiners Position Paper
Authors: Utley Suzanne , Arunkumar Ponni , Das Tara , Fierro Marcella F. , Fudenberg John , Harding Brett E. , Hoffmann Bryan A. , Keyes Kelly A. , Lewis Adele , Maloney Katherine , O'Neal Bobbi Jo , Pinneri Kathryn , Rapkiewicz Amy , Sathyavagiswaran Lakshmanan , Weedn Victor , Williams Tiffany
Published: August 2023

Collecting and reporting accurate disaster mortality data are critical to informing disaster response and recovery efforts. The National Association of Medical Examiners convened an ad hoc committee to provide recommendations for the documentation and certification of disaster-related deaths. This article provides definitions for disasters and direct, indirect, and partially attributable disaster-related deaths; discusses jurisdiction for disaster-related deaths; offers recommendations for medical examiners/coroners (ME/Cs) for indicating the involvement of the disaster on the death certificate; discusses the role of the ME/C and non-ME/C in documenting and certifying disaster-related deaths; identifies existing systems for helping to identify the role of disaster on the death certificate; and describes disaster-related deaths that may require amendments of death certificates. The recommendations provided in this article seek to increase ME/C's understanding of disaster-related deaths and promote uniformity in how to document these deaths on the death certificate.
Neonatal complicated intraabdominal infection
Authors: Rauh Jessica L. , Lehane Alison J. , Sieren Leah M. , Neff Lucas P.
Published: August 2023

Purpose of review

The purpose of this review is to summarize the treatment of complicated intraabdominal infections (cIAIs) in premature infants.

Recent findings

Recent work has continued to define the complex nature of cIAIs and necrotizing enterocolitis (NEC). This includes new findings on the microbiome, breast milk and risk factors associated with NEC. The treatment of cIAIs employs a combination of both surgical and medical treatment. Further look at what type and timing of surgical intervention is used as well as the ideal antibiotic regimen. Upcoming research is highlighted in future directions of NEC treatment.

cIAIs in premature infants is a challenging disease with more research needed to further delineate the pathophysiology and treatment options.
A Prospective Cohort Analysis of the Prevalence and Predictive Factors of Delayed Discharge After Laparoscopic Cholecystectomy in Italy: The DeDiLaCo Study
Authors: Cillara Nicola , Podda Mauro , Cicalò Enrico , Sotgiu Giovanni , Provenzano Maria , Fransvea Pietro , Poillucci Gaetano , Sechi Raffaele ,   the DeDiLaCo Study Collaborative Group
Published: August 2023

Background:

The concept of early discharge ≤24 hours after Laparoscopic Cholecystectomy (LC) is still doubted in Italy. This prospective multicentre study aims to analyze the prevalence of patients undergoing elective LC who experienced a delayed discharge >24 hours in an extensive Italian national database and identify potential limiting factors of early discharge after LC.

Methods:

This is a prospective observational multicentre study performed from January 1, 2021 to December 31, 2021 by 90 Italian surgical units.

Results:

A total of 4664 patients were included in the study. Clinical reasons were found only for 850 patients (37.7%) discharged >24 hours after LC. After excluding patients with nonclinical reasons for delayed discharge >24 hours, 2 groups based on the length of hospitalization were created: the Early group (≤24 h; 2414 patients, 73.9%) and the Delayed group (>24 h; 850 patients, 26.1%). At the multivariate analysis, ASA III class (P<0.0001), Charlson’s Comorbidity Index (P=0.001), history of choledocholithiasis (P=0.03), presence of peritoneal adhesions (P<0.0001), operative time >60 min (P<0.0001), drain placement (P<0.0001), pain (P=0.001), postoperative vomiting (P=0.001) and complications (P<0.0001) were independent predictors of delayed discharge >24 hours.

Conclusions:

The majority of delayed discharges >24 hours after LC in our study were unrelated to the surgery itself. ASA class >II, advanced comorbidity, the presence of peritoneal adhesions, prolonged operative time, and placement of abdominal drainage were intraoperative variables independently associated with failure of early discharge.
Tacrolimus After rATG and Infliximab Induction Immunosuppression—RIMINI Trial
Authors: Viklicky Ondrej , Zahradka Ivan , Bold Gantuja , Bestard Oriol , Hruba Petra , Otto Natalie M. , Stein Maik , Sefrin Anett , Modos Istvan , Meneghini Maria , Crespo Elena , Grinyo Josep , Volk Hans-Dieter , Christakoudi Sofia , Reinke Petra
Published: August 2023

Background.

Infliximab selectively targets recently activated effector cells and, as an induction agent, might enable the safe elimination of mycophenolate from maintenance immunosuppression in kidney transplantation.

Methods.

This is a phase II international multicenter open-label single-arm confidence interval (CI)–based clinical trial of the BIO-DrIM EU consortium aimed at assessing the efficacy and safety of rabbit antithymocyte globulin and infliximab induction in kidney transplantation. Sixty-seven primary kidney transplant recipients at low risk (panel-reactive antibodies <20%, no donor-specific antibodies [DSA]) received rabbit antithymocyte globulin (2 × 1.5 mg/kg, postoperative days 0 and 1) and infliximab (5 mg/kg, postoperative day 2), followed by mycophenolate-free tacrolimus-based immunosuppression for 12 mo. The primary endpoint was efficacy failure, defined as a composite of acute rejection, graft loss, or poor graft function (estimated glomerular filtration rate <40 mL/min) at 12 mo and was based on the endpoint of the comparator study. Additionally, a historical propensity-matched control cohort was established.

Results.

Primary endpoint occurred in 22 of 67 patients (32.84%), with upper bound of an exact 1-sided 95% CI of 43.47%, which met the predefined criteria (efficacy failure of <40% and upper-bound 95% CI of <50%) and was similar in the historical matched cohort. By 12 mo, 79.1% of patients remained on the study protocol. Lower rates of BK replication (6% versus 22.4%; P = 0.013) but higher rates of de novo DSAs (11.9% versus 1.5%; P = 0.039) were observed in the study cohort.

Conclusions.

A similar efficacy of the study immunosuppression regimen to the comparator study and the historical matched cohort was found. However, a higher de novo DSA emergence points to an increased risk of antibody-mediated rejection (NCT04114188).
SalmonellaInfantis, the emerging human multidrug resistant pathogen – a One Health perspective
Authors: Mattock Jennifer , Chattaway Marie Anne , Hartman Hassan , Dallman Timothy J. , Smith Anthony M. , Keddy Karen , Petrovska Liljana , Manners Emma J. , Duze Sanelisiwe T. , Smouse Shannon , Tau Nomsa , Timme Ruth , Baker Dave J. , Mather Alison E. , Wain John , Langridge Gemma C.
Published: August 2023

Salmonella Infantis presents an ever-increasing threat to public health due to its spread throughout many countries and association with high levels of antimicrobial resistance (AMR). Whole genome sequences of 5,284S. Infantis strains from 74 countries, isolated between 1989 and 2020 from a wide variety of sources including humans, animals, and food, were analysed to compare genetic phylogeny, AMR determinants and plasmid presence.

The globalS. Infantis population structure diverged into three clusters: a North American cluster, European cluster and a global cluster. The levels of AMR varied between theS. Infantis clusters and by isolation source; 73% of poultry isolates had multidrug resistance (MDR) compared to 35% of human isolates. This correlated with plasmid of emergingS. Infantis (pESI) presence; 71% of poultry isolates contained pESI versus 32% of human isolates. This provides important information for public health teams engaged in reducing the spread of this pathogen.
ATML1 Regulates the Differentiation of ER Body-containing Large Pavement Cells in Rosette Leaves of Brassicaceae Plants
Authors: Wilkens Alwine , Czerniawski Paweł , Bednarek Paweł , Libik-Konieczny Marta , Yamada Kenji
Published: August 2023

Endoplasmic reticulum (ER)-derived organelles, ER bodies, participate in the defense against herbivores in Brassicaceae plants. ER bodies accumulate β-glucosidases, which hydrolyse specialized thioglucosides known as glucosinolates to generate bioactive substances. InArabidopsis thaliana, the leaf ER (LER) bodies are formed in large pavement cells, which are found in the petioles, margins, and blades of rosette leaves. However, the regulatory mechanisms involved in establishing large pavement cells are unknown. Here, we show that the ARABIDOPSIS THALIANA MERISTEM L1 LAYER (ATML1) transcription factor regulates the formation of LER bodies in large pavement cells of rosette leaves. Overexpression ofATML1enhanced the expression of LER body-related genes and the number of LER body-containing large pavement cells, whereas its knockout resulted in opposite effects. ATML1 enhances endoreduplication and cell size through LOSS OF GIANT CELLS FROM ORGANS (LGO). Although the overexpression and knockout ofLGOaffected the appearance of large pavement cells in Arabidopsis, the effect on LER body-related gene expression and LER body formation was weak. LER body-containing large pavement cells were also found inEutrema salsugineum, another Brassicaceae species. Our results demonstrate that ATML1 establishes large pavement cells to induce LER body formation in Brassicaceae plants, contributing to the defense against herbivores.
QJHong Model for Novel Coronavirus Disease 2019 (COVID-19) in the United States
Authors: Mehta Aanand , Hong Qi-Jun
Published: August 2023

We present the methodology of the QJHong model, a machine learning predictive model we built to forecast the COVID-19 daily cases, number of daily deaths, fatality rate, reproductive number, and overall trends in the United States (both national and individual states). We measure the accuracy and compare it to other predictive models. Several forecast analyses consistently demonstrate that the QJHong model outperforms other models submitted to the COVID-19 Forecast Hub with regards to forecasting national data. The Forecast Hub is utilized by the Centers for Disease Control and Prevention (CDC) as a means of disseminating official public communications pertaining to the ongoing pandemic. As such, our model has been identified as a premier performer within this context.
Potential to Enhance Large Scale Molecular Assessments of Skin Photoaging through Virtual Inference of Spatial Transcriptomics from Routine Staining
Authors: Srinivasan Gokul , Davis Matthew , LeBoeuf Matthew , Fatemi Michael , Azher Zarif , Lu Yunrui , Diallo Alos , Montivero Marietta Saldias , Kolling Fred , Perrard Laurent , Salas Lucas , Christensen Brock , Palisoul Scott , Tsongalis Gregory , Vaickus Louis , Preum Sarah , Levy Joshua
Published: August 2023

The advent of spatial transcriptomics technologies has heralded a renaissance in research to advance our understanding of the spatial cellular and transcriptional heterogeneity within tissues. Spatial transcriptomics allows investigation of the interplay between cells, molecular pathways and the surrounding tissue architecture and can help elucidate developmental trajectories, disease pathogenesis, and various niches in the tumor microenvironment. Photoaging is the histological and molecular skin damage resulting from chronic/acute sun exposure and is a major risk factor for skin cancer. Spatial transcriptomics technologies hold promise for improving the reliability of evaluating photoaging and developing new therapeutics. Current challenges, including limited focus on dermal elastosis variations and reliance on self-reported measures, can introduce subjectivity and inconsistency. Spatial transcriptomics offer an opportunity to assess photoaging objectively and reproducibly in studies of carcinogenesis and discern the effectiveness of therapies that intervene on photoaging and prevent cancer. Evaluation of distinct histological architectures using highly-multiplexed spatial technologies can identify specific cell lineages that have been understudied due to their location beyond the depth of UV penetration. However, the cost and inter-patient variability using state-of-the-art assays such as the 10x Genomics Spatial Transcriptomics assays limits the scope and scale of large-scale molecular epidemiologic studies. Here, we investigate the inference of spatial transcriptomics information from routine hematoxylin and eosin-stained (H&E) tissue slides. We employed the Visium CytAssist spatial transcriptomics assay to analyze over 18,000 genes at a 50-micron resolution for four patients from a cohort of 261 skin specimens collected adjacent to surgical resection sites for basal and squamous keratinocyte tumors. The spatial transcriptomics data was co-registered with 40x resolution whole slide imaging (WSI) information. We developed machine learning models that achieved a macro-averaged median AUC and F1 score of 0.80 and 0.61 and Spearman coefficient of 0.60 in inferring transcriptomic profiles across the slides, and accurately captured biological pathways across various tissue architectures.
EstablishingAc/DsStarter Lines for Large-Scale Transposon-Tagged Mutagenesis in Tomato
Authors: Kumari Alka , Ponukumatla Rachana , Pandey Arun Kumar , Sreelakshmi Yellamaraju , Sharma Rameshwar
Published: August 2023

Tomato (Solanum lycopersicum), a model system for ripening of fleshy fruits, has ∼40,000 genes predicted byin silicohomology-based annotation. However, functional validation is lacking for most annotated tomato genes. Among the strategies for functional annotations, transposon-tagged mutagenesis is the most powerful approach. Transposon- tagged genes can be functionally validated by phenotyping and activation tagging. However, the lack of a robustin plantatransformation system precludes large-scale transposon- mutagenesis of tomato. To overcome this limitation, we developed two sets of starter lines in tomato, each carrying maize transposon element (Ds) and transposase (Ac), respectively. TheDsandAclines were crossed to allow theAc-mediated transposition of theDsin the F1generation. In the F2generation, the location of excisedDsat new sites in the tomato genome was monitored. TheDstransposition was interspersed on different chromosomes of the tomato, indicating unlinked transposition of theDs. The analysis of DNA sequences flankingDsshowed random integration ofDsin intergenic, genes, and the promoter region of the genome. Our study paves the way for the generation of large-scale transposon-tagged tomato lines usingAc/Dsstarter lines and provides a potential tool for the functional validation of genes in tomato.

Short summary

We developed two sets of starter lines in tomato, carrying maize transposon element (Ds) and transposase (Ac), to enable large-scale transposon-mutagenesis, facilitating functional validation of tomato genes and for generating an insertional mutant resource in tomato.
Protein kinase PfPK2 mediated signalling is critical for host erythrocyte invasion by malaria parasite
Authors: Rawat Rahul Singh , Gupta Ankit , Antil Neelam , Bhatnagar Sonika , Prasad T.S. Keshava , Sharma Pushkar
Published: August 2023

Signalling pathways in malaria parasite remain poorly defined and major reason for this is the lack of understanding of the function of majority of parasite protein kinases and phosphatases in parasite signalling and its biology. In the present study, we have elucidated the function of Protein Kinase 2 (PfPK2), which is known to be indispensable for the survival of human malaria parasitePlasmodium falciparum. We demonstrate that it is involved in the invasion of host erythrocytes, which is critical for establishing infection. In addition, PfPK2 may also be involved in the maturation of the parasite post-invasion. PfPK2 regulates the release of microneme proteins like Apical Membrane Antigen 1 (AMA1), which facilitates the formation of Tight Junction between the merozoite and host erythrocyte-a key step in the process of invasion. Comparative phosphoproteomics studies revealed that PfPK2 may be involved in regulation of several key proteins involved in invasion and signalling. Furthermore, PfPK2 regulates the generation of cGMP and the release of calcium in the parasite, which are key second messengers for the process of invasion. These and other studies have shed light on a novel signalling pathway in which PfPK2 acts as an upstream regulator of important cGMP-calcium signalling, which is plays an important role in parasite invasion.
Pleiotropic effects of trisomy and pharmacologic modulation on structural, functional, molecular, and genetic systems in a Down syndrome mouse model
Authors: Llambrich Sergi , Tielemans Birger , Saliën Ellen , Atzori Marta , Wouters Kaat , Van Bulck Vicky , Platt Mark , Vanherp Laure , Gallego Fernandez Nuria , Grau de la Fuente Laura , Poptani Harish , Verlinden Lieve , Himmelreich Uwe , Croitor Anca , Attanasio Catia , Callaerts-Vegh Zsuzsanna , Gsell Willy , Martínez-Abadías Neus , Vande Velde Greetje
Published: August 2023

Down syndrome (DS) is characterized by skeletal and brain structural malformations, cognitive impairment, altered hippocampal metabolite concentration and gene expression imbalance. These alterations were usually investigated separately, and the potential rescuing effects of green tea extracts enriched in epigallocatechin-3-gallate (GTE-EGCG) provided disparate results due to different experimental conditions. We overcame these limitations by conducting the first longitudinal controlled experiment evaluating genotype and GTE-EGCG prenatal chronic treatment effects before and after treatment discontinuation. Our findings revealed that the Ts65Dn mouse model reflected the pleiotropic nature of DS, exhibiting brachycephalic skull, ventriculomegaly, neurodevelopmental delay, hyperactivity, and impaired memory robustness with altered hippocampal metabolite concentration and gene expression. GTE-EGCG treatment modulated most systems simultaneously but did not rescue DS phenotypes. On the contrary, the treatment exacerbated trisomic phenotypes including body weight, tibia microarchitecture, neurodevelopment, adult cognition, and metabolite concentration, not supporting the therapeutic use of GTE-EGCG as a prenatal chronic treatment. Our results highlight the importance of longitudinal experiments assessing the co-modulation of multiple systems throughout development when characterizing preclinical models in complex disorders and evaluating the pleiotropic effects and general safety of pharmacological treatments.
Multiple host targets ofPseudomonaseffector protein HopM1 form a protein complex regulating apoplastic immunity and water homeostasis
Authors: Nomura Kinya , Imboden Lori Alice , Tanaka Hirokazu , He Sheng Yang
Published: August 2023

Bacterial type III effector proteins injected into the host cell play a critical role in mediating bacterial interactions with plant and animal hosts. Notably, some bacterial effectors are reported to target sequence-unrelated host proteins with unknown functional relationships. ThePseudomonas syringaeeffector HopM1 is such an example; it interacts with and/or degrades several HopM1-interacting (MIN) Arabidopsis proteins, including HopM1-interacting protein 2 (MIN2/RAD23), HopM1-interacting protein 7 (MIN7/BIG5), HopM1-interacting protein 10 (MIN10/14-3-3ĸ), and HopM1-interacting protein 13 (MIN13/BIG2). In this study, we purified the MIN7 complex formedin plantaand found that it contains MIN7, MIN10, MIN13, as well as a tetratricopeptide repeat protein named HLB1. Mutational analysis showed that, like MIN7, HLB1 is required for pathogen-associated molecular pattern (PAMP)-, effector-, and benzothiadiazole (BTH)-triggered immunity. HLB1 is recruited to the trans-Golgi network (TGN)/early endosome (EE) in a MIN7-dependent manner. Bothmin7andhlb1mutant leaves contained elevated water content in the leaf apoplast and artificial water infiltration into the leaf apoplast was sufficient to phenocopy immune-suppressing phenotype of HopM1. These results suggest that multiple HopM1-targeted MIN proteins form a protein complex with a dual role in modulating water level and immunity in the apoplast, which provides an explanation for the dual phenotypes of HopM1 during bacterial pathogenesis.
Mass spectrometry-based multi-omics identifies metabolic signatures of sarcopenia in rhesus monkey skeletal muscle
Authors: Pergande Melissa R , Osterbauer Katie J , Buck Kevin M , Roberts David S , Wood Nina N , Balasubramanian Priya , Mann Morgan W , Rossler Kalina , Diffee Gary M , Colman Ricki J , Anderson Rozalyn M , Ge Ying
Published: August 2023

Sarcopenia is a progressive disorder characterized by age-related loss of skeletal muscle mass and function. Although significant progress has been made over the years to identify the molecular determinants of sarcopenia, the precise mechanisms underlying the age-related loss of contractile function remains unclear. Advances in omics technologies, including mass spectrometry-based proteomic and metabolomic analyses, offer great opportunities to better understand sarcopenia. Herein, we performed mass spectrometry-based analyses of the vastus lateralis from young, middle-aged, and older rhesus monkeys to identify molecular signatures of sarcopenia. In our proteomic analysis, we identified numerous proteins that change with age, including those involved in adenosine triphosphate and adenosine monophosphate metabolism as well as fatty acid beta oxidation. In our untargeted metabolomic analysis, we identified multiple metabolites that changed with age largely related to energy metabolism including fatty acid beta oxidation. Pathway analysis of age-responsive proteins and metabolites revealed changes in muscle structure and contraction as well as lipid, carbohydrate, and purine metabolism. Together, this study discovers new metabolic signatures and offer new insights into the molecular mechanism underlying sarcopenia for the evaluation and monitoring of therapeutic treatment of sarcopenia.
Probing Bioactive Chemical Space to Discover RNA-Targeted Small Molecules
Authors: Wicks Sarah L. , Morgan Brittany S. , Wilson Alexander W. , Hargrove Amanda E.
Published: August 2023

Small molecules have become increasingly recognized as invaluable tools to study RNA structure and function and to develop RNA-targeted therapeutics. To rationally design RNA-targeting ligands, a comprehensive understanding and explicit testing of small molecule properties that govern molecular recognition is crucial. To date, most studies have primarily evaluated properties of small molecules that bind RNAin vitro, with little to no assessment of properties that are distinct to selective and bioactive RNA-targeted ligands. Therefore, we curated an RNA-focused library, termed theDukeRNA-TargetedLibrary (DRTL), that was biased towards the physicochemical and structural properties of biologically active and non-ribosomal RNA-targeted small molecules. The DRTL represents one of the largest academic RNA-focused small molecule libraries curated to date with more than 800 small molecules. These ligands were selected using computational approaches that measure similarity to known bioactive RNA ligands and that diversify the molecules within this space. We evaluated DRTL bindingin vitroto a panel of four RNAs using two optimized fluorescent indicator displacement assays, and we successfully identified multiple small molecule hits, including several novel scaffolds for RNA. The DRTL has and will continue to provide insights into biologically relevant RNA chemical space, such as the identification of additional RNA-privileged scaffolds and validation of RNA-privileged molecular features. Future DRTL screening will focus on expanding both the targets and assays used, and we welcome collaboration from the scientific community. We envision that the DRTL will be a valuable resource for the discovery of RNA-targeted chemical probes and therapeutic leads.
Nonlethal Blood Sampling from the KillifishNothobranchius furzeri
Authors: Dolfi Luca , Ripa Roberto , Medelbekova Danel , Ballhysa Eugen , Symmons Orsolya , Antebi Adam
Published: August 2023

Blood withdrawal is a common procedure performed on laboratory animals to monitor key processes and indicators of fish health and physiology, such as hematopoiesis, hemostasis, and lipid and glucose metabolism. Moreover, the ability to extract blood with minimal invasiveness and without sacrificing animals enables repeated sampling, allowing both longitudinal studies of individual animals, as well as reducing the number of experimental animals needed in a study. The African turquoise killifish is an emerging animal model that is progressively being adopted worldwide for aging studies because of its naturally short life span. However, because of the small body size of this species, nonlethal blood collection is a challenging procedure. Here we present a detailed protocol enabling repeated blood sampling from the same individual fish. This method, if correctly executed, is minimally invasive and does not cause any lasting damage. The protocol has been tested on animals spanning from 6 to 24 wk of age and the amount of blood that could be extracted varied from 0.5 to 8 µL, greatly depending on specimen age, sex, and size. This volume is sufficient to perform analyses such as blood glucose measurement, blood cell counts, or histological stains on blood smears.
Micro-CT Analysis of Fat in the KillifishNothobranchius furzeri
Authors: Ripa Roberto , Mesaros Andrea , Symmons Orsolya , Ballhysa Eugen , Dolfi Luca , Antebi Adam
Published: August 2023

Aging is associated with an increase in body fat mass and a concomitant decrease in lean mass and bone density in mammals. Body adiposity can also be redistributed with age, resulting in abdominal fat accumulation and subcutaneous fat reduction. In addition, specific variation in fat distribution is considered to be a risk factor for a number of age-related metabolic disorders. Micro computed tomography (micro-CT) is a nondestructive high-resolution imaging method that uses planar X-ray images captured at various angles around a sample of interest to yield a three-dimensional array of radiodensity values, which can then be used to computationally extract the adipose volume in situ using its innate contrast properties. This method was successfully used to study adipose tissue dynamics in rodents and more recently in zebrafish. The naturally short-lived African turquoise killifish is an emerging model organism to study the biology of aging. Like mammals, killifish also have different fat deposits (visceral and subcutaneous), making them a suitable model to study age-related changes in fat mass and distribution. However, procedures allowing precise quantification of fat content and distribution are missing in this species. Here, we provide an optimized protocol to measure and quantify fat distribution in turquoise killifish by micro-CT scan analysis and show the applicability of the method in young and old animals of both sexes.