bluuebunny/crossref_metadata_2025 huggingface dataset:
Antibiotic Recommendations After Postpartum Uterine Exploration or Instrumentation
Authors: Lambert Katherine A. , Honart Anne West , Hughes Brenna L. , Kuller Jeffrey A. , Dotters-Katz Sarah K.
Published: July 2023

Importance

Multiple postpartum scenarios require uterine exploration or instrumentation. These may introduce bacteria into the uterus, increasing the risk of endometritis. Data on the use of antibiotics in these scenarios is limited, resulting in few guidelines and divergent care.

Objective

To describe postpartum scenarios requiring uterine exploration and/or instrumentation, review data on antibiotic prophylaxis, and delineate antibiotic recommendations for each scenario.

Evidence Acquisition

Original articles were obtained from literature search in PubMed, MEDLINE, and OVID; pertinent articles were reviewed.

Results

These recommendations are based on published evidence and professional society guidelines. Antibiotic prophylaxis following manual placenta removal should include 1-time combination of ampicillin 2 g intravenously (IV) or cefazolin 1 g IV, plus metronidazole 500 mg IV. Antibiotic prophylaxis before postpartum dilation and curettage, manual vacuum aspiration, and intrauterine balloon tamponade should include 1-time combination of ampicillin 2 g IV plus metronidazole 500 mg IV. If the patient in any of the above scenarios has received group B Streptococcus prophylaxis, then only metronidazole is recommended. Further randomized clinical trials are needed to optimize these regimens.

Conclusions

Uterine exploration or instrumentation increases the risk of postpartum endometritis and requires antibiotic prophylaxis. For manual placenta removal, we recommend 1-time combination of ampicillin 2 g IV or cefazolin 1 g IV, plus metronidazole 500 mg IV. For dilation and curettage, manual vacuum aspiration, and intrauterine balloon tamponade, we recommend 1-time combination of ampicillin 2 g IV plus metronidazole 500 mg IV. For patients who already received antibiotic prophylaxis for group B Streptococcus, we recommend 1-time dose of metronidazole 500 mg IV.

Relevance

Providers can utilize our guidelines to prevent postpartum endometritis in these scenarios requiring postpartum uterine exploration and/or instrumentation.

Target Audience

Obstetricians and gynecologists, family physicians

Learning Objectives

After reading this article, the provider should be better able to discuss diagnosis and management of endometritis; describe antibiotic regimens recommended in the setting of uterine exploration postpartum; and identify antibiotic regimens recommended in the setting of postpartum uterine instrumentation.
Concurrent Surgery for Locoregional Gynecologic Cancers and Pelvic Floor Disorders in a Population of Patients With Medicare Insurance
Authors: Corey Logan , Seaton Randell , Ruterbusch Julie J. , Bretschneider Carol Emi , Vezina Alex , Do Trieu , Hobson Deslyn , Winer Ira
Published: July 2023

(Abstracted from Obstet Gynecol 2023;141:629–641)

Most women diagnosed with a gynecologic cancer report symptoms related to pelvic organ prolapse or urinary incontinence (POP-UI) before and during their cancer treatment. Often, these symptoms go untreated; however, several studies have suggested concurrent surgery for gynecologic cancer, and POP-UI symptoms is safe and may reduce total surgeries but lack long-term follow-up data.
Cell-Free DNA in Maternal Blood and Artificial Intelligence: Accurate Prenatal Detection of Fetal Congenital Heart Defects
Authors: Bahado-Singh Ray , Friedman Perry , Talbot Ciara , Aydas Buket , Southekal Siddesh , Mishra Nitish K. , Guda Chittibabu , Yilmaz Ali , Radhakrishna Uppala , Vishweswaraiah Sangeetha
Published: July 2023

(Abstracted from Am J Obstet Gynecol 2023;228(1):76.e1–76.e10)

Congenital heart defects (CHDs) are one of the leading causes of child morbidity and mortality. Previous research has shown that prenatal detection of CHD can significantly reduce the risk of death for severe cases, yet the current techniques available for prenatal diagnosis detect approximately only half of cases.
Centering Group Treatment for Women With Interstitial Cystitis/Bladder Pain Syndrome: A Prospective, Parallel-Group Cohort Study
Authors: Meriwether Kate V. , Ravichandran Niharika , Darley Cassandra J. , Panter Virginia , Komesu Yuko M.
Published: July 2023

(Abstracted from Urogynecology 2023;29:410–421)

Although difficult to diagnose and measure, interstitial cystitis/bladder pain syndrome (ICBPS) affects up to 1 in 10 women (with even higher rates amid pelvic pain populations). This condition causes shame and stigma for its victims, leading to isolation, loneliness, and compromised ability to voice personal needs.
Diagnosis and Management of Prediabetes: A Review
Authors: Echouffo-Tcheugui Justin B. , Perreault Leigh , Ji Linong , Dagogo-Jack Sam
Published: July 2023

(Abstracted from JAMA 2023;329(14):1206–1216)

Prediabetes is a highly prevalent intermediate stage of glucose dysregulation that may precede type 2 diabetes. In the United States, approximately 10% of those with prediabetes will develop diabetes each year, and the prevalence of prediabetes is steadily increasing.
Durable Vascular Access in Neonates in the Cardiac ICU: A Novel Technique for Tunneled Femoral Central Venous Catheters*
Authors: Mills Marcos , Chanani Nikhil , Wolf Michael , Bauser-Heaton Holly , Beshish Asaad , Aljiffry Alaa , Zinyandu Tawanda , Maher Kevin
Published: July 2023

OBJECTIVES:

There is an ongoing need for a method of obtaining long-term venous access in critically ill pediatric patients that can be completed at the bedside and results in a durable, highly functional device. We designed a novel technique for tunneled femoral access to address this need. Herein, we describe the procedure and review the outcomes at our institution.

DESIGN:

A single-center retrospective chart review identifying patients who underwent tunneled femoral central venous catheter (tfCVC) placement between 2017 and 2021 using a two-puncture technique developed by our team.

SETTING:

Academic, Quaternary Children’s Hospital with a dedicated pediatric cardiac ICU (CICU).

PATIENTS:

Patients in our pediatric CICU who underwent this procedure.

INTERVENTIONS:

Tunneled femoral central line placement.

MEASUREMENTS AND MAIN RESULTS:

One hundred eighty-two encounters were identified in 161 patients. The median age and weight at the time of catheter placement was 22 days and 3.2 kg. The median duration of the line was 22 days. The central line-associated bloodstream infection (CLABSI) rate was 0.75 per 1,000-line days. The prevalence rate of thrombi necessitating pharmacologic treatment was 2.0 thrombi per 1,000-line days. There was no significant difference in CLABSI rate per 1,000-line days between the tfCVC and nontunneled peripherally inserted central catheters placed over the same period in a similar population (−0.40 [95% CI, −1.61 to 0.82; p = 0.52]) and no difference in thrombus rates per 1,000-line days (1.37 [95% CI, −0.15 to 2.89; p = 0.081]).

CONCLUSIONS:

tfCVCs can be placed by the intensivist team using a two-puncture technique at the bedside with a high-rate of procedural success and low rate of complications. Advantages of this novel technique of obtaining vascular access include a low rate of CLABSIs, the ability to place it at the bedside, and preservation of the upper extremity vasculature.
Agenesis of the Dorsal Pancreas: Case Report and Review of Age-Related Differences in Presentation
Authors: Grey Callie A. , Desai Ajinkya , Nowicki Michael J. , Bhesania Natalie
Published: July 2023

Agenesis of the dorsal pancreas (ADP) is a rare congenital anomaly that occurs when the body and tail of the pancreas fail to develop from the dorsal bud in utero. ADP may be discovered when evaluating conditions arising from the anomaly, such as diabetes mellitus, pancreatitis, and pancreatic insufficiency, but is more commonly found as an incidental finding. To date, fewer than 120 cases have been reported in the literature. We report a 6-year-old male who was found to have ADP on computed tomography during the investigation of abdominal pain and vomiting. We review the variable presentation, genetic mutations, and age-related differences between children and adults with this rare condition.
Wolfram Syndrome-2, a Cause of Severe Gastrointestinal Bleeding: A Case Series and a Literature Review
Authors: Ateya Rania , Ciecierega Thomas , Abusamra Muttaz , Abuawwad Motee , Abu-Libdeh Abdulsalam , Sultan Mutaz
Published: July 2023

Background:

There are very few reports of Wolfram syndrome-2 (WFS2) in the literature, and understanding of involvement of the gastrointestinal (GI) tract in the syndrome is limited. Objectives: This study aims to describe the clinical presentations of a large number of WFS2 patients with specific focus on their GI manifestations.

Methods:

This is a retrospective case series study. Patients who were homozygous for the CISD2 gene mutation were identified through the genetic department of Al-Makassed hospital. Their medical records were reviewed, and biometric data have been obtained. The data were collected and arranged on a data sheet, and descriptive analysis was done using SPSS.

Results:

Thirteen patients from 9 families were identified; diabetes mellitus was present in 6 of them, optic atrophy in 5, diabetes insipidus (DI) in 5, and deafness in 2. All of the patients had GI manifestations with abnormal findings on upper endoscopy. Dysmorphic facial features and abnormal findings on brain MRI were present in 3 of our patients. The GI manifestations including GI bleeding and severe ulcerations were the first to appear in 9 of them, while anemia in the remaining 4.

Conclusion:

This is the largest study to date describing patients with WFS2. This study’s evidence shows the prominent presence of GI involvement, and the severe findings on endoscopy, including duodenal, gastric, and esophageal ulcerations and strictures. Unlike in the Jordanian report, some of the patients in our report also have DI.
Food for Thought: Remission of Perianal Pediatric Crohn’s Disease on Specific Carbohydrate Diet Monotherapy
Authors: Simon David , Patel Kalyani , Masand Prakash , Kellermayer Richard
Published: July 2023

There is growing interest among patients about the specific carbohydrate diet (SCD) as a treatment for Crohn’s disease. In the meantime, deep remission in patients using SCD as their sole treatment has not been documented. We report a case with perianal and ileocolonic Crohn’s disease in whom SCD monotherapy successfully induced and maintained not only clinical, but also endoscopic, radiographic and histologic (ie, deep mucosal remission) remission as well.
Myocardial Injury After Noncardiac Surgery in Major General Surgical Patients A Prospective Observational Cohort Study
Authors: Jacka Michael J , Youngson Erik , Bigam David , Graham Michelle M. , Heels-Ansdell Diane , Jaeyoung Park Lily , Bendtz Kanstrup Charlotte Tiffanie , Nenshi Rahima , Bagshaw Sean M , McAlister Finlay , Pannu Neesh , Townsend Derek , McMurtry Michael S. , Devereaux Philip J.
Published: July 2023

Objective:

to determine the prognostic relevance, clinical characteristics, and 30-day outcomes associated with myocardial injury after noncardiac surgery (MINS) in major general surgery patients.

Background:

MINS has been independently associated with 30-day mortality after noncardiac surgery. The characteristics and prognostic importance of MINS in major general surgical patients have not been described.

Methods:

This was an international prospective cohort study of a representative sample of 22,552 noncardiac surgery patients 45 years or older, of whom 4490 underwent major general surgery in 24 centers in 13 countries. All patients had fifth-generation plasma high-sensitivity troponin T (hsTnT) concentrations measured during the first three postoperative days. MINS was defined as a hsTnT of 20–65 ng/L and absolute change >5 ng/L or hsTnT ≥65 ng/L secondary to ischemia. The objectives of the present study were to determine (i) whether MINS is prognostically important in major general surgical patients, (ii) the clinical characteristics of major general surgical patients with and without MINS, (iii) the 30-day outcomes for major general surgical patients with and without MINS, and (iv) the proportion of MINS that would have gone undetected without routine postoperative monitoring.

Results:

The incidence of MINS in the major general surgical patients was 16.3% (95% confidence interval (CI), 15.3–17.4%). 30-day all-cause mortality in the major general surgical cohort was 6.8% (95% CI 5.1%–8.9%) in patients with MINS compared with 1.2% (95% CI 0.9%–1.6%) in patients without MINS (P<0.01). MINS was independently associated with 30-day mortality in major general surgical patients (adjusted odds ratio 4.7, 95% CI 3.0–7.4). The 30-day mortality was higher both among MINS patients with no ischemic features (i.e., no ischemic symptoms or electrocardiogram findings) (5.4%, 95% CI 3.7–7.7%) and among patients with 1 or more clinical ischemic features (10.6%, 95% CI 6.7–15.8%). The proportion of major general surgical patients who had MINS without ischemic symptoms was 89.9% (95% CI 87.5–92.0).

Conclusions:

Approximately 1 in 6 patients experienced MINS after major general surgery. MINS was independently associated with a nearly five-fold increase in 30-day mortality. The vast majority of patients with MINS were asymptomatic and would have gone undetected without routine postoperative troponin measurement.
Complications After Uterosacral Ligament Suspension Versus Sacrospinous Ligament Fixation at Vaginal Hysterectomy: A Retrospective Cohort Study of the National Surgical Quality Improvement Program Database
Authors: Stairs Jocelyn , Jain Mehr , Chen Innie , Clancy Aisling
Published: July 2023

Importance

Apical suspension, including uterosacral ligament suspension (USLS) and sacrospinous ligament fixation (SSLF), is the standard of care at vaginal hysterectomy. Although the equivalence of anatomic and clinical outcomes after USLS and SSLF is established, comparing surgical complications specific to patients undergoing concurrent vaginal hysterectomy further informs decision making regarding operative approach.

Objective

This study aims to compare complications in the first 30 days after surgery in patients undergoing USLS and SSLF at vaginal hysterectomy for pelvic organ prolapse.

Study Design

This retrospective, population-based cohort study used the American College of Surgeons National Surgical Quality Improvement Program database to identify patients undergoing USLS or SSLF at vaginal hysterectomy for pelvic organ prolapse between 2012 and 2019. The primary outcome was a composite of surgical complications excluding urinary tract infection (UTI). Odds of the primary outcome, readmission, reoperation, and UTI were evaluated by multivariable logistic regression models.

Results

Of 10,210 eligible patients, 7,127 patients underwent USLS and 3,083 patients underwent SSLF. Uterosacral ligament suspension was associated with a 25% lower odds of the composite complication outcome that excluded UTI compared with SSLF (adjusted odds ratio, 0.75; 95% confidence interval, 0.63–0.90). Urinary tract infection was the most common complication and occurred more commonly in patients undergoing USLS (6.5% vs 4.9%; adjusted odds ratio, 1.29; 95% confidence interval, 1.06–1.56). There was no significant difference in Clavien-Dindo class IV complications, readmission, or reoperation between approaches.

Conclusion

Uterosacral ligament suspension was associated with a lower odds of complications excluding UTI compared with SSLF. Urinary tract infection was more common among patients having USLS. The odds of serious complications, readmission, and reoperation were low and comparable between groups.
Examining Age and Postoperative Opioid Use in the Urogynecology Population: A Prospective Study
Authors: Willis-Gray Marcella G. , Leazer Haley A. , Sun Stephanie , Feliciano Katherine M. , Dieter Alexis A. , Geller Elizabeth J. , Connolly AnnaMarie , Chidgey Brooke A. , Wu Jennifer M.
Published: July 2023

Importance

Surgeons must individualize postoperative pain management while also reducing the amount of unused prescribed opioids.

Objectives

This study compared postoperative opioid use in younger versus older women following urogynecologic surgery. We also assessed the likelihood of women returning unused opioids for safe disposal.

Study Design

This was a prospective study of women undergoing pelvic reconstructive surgery divided into 2 cohorts: younger (<65 years) and older (≥65 years). Our primary outcome was total opioid use, measured in morphine milligram equivalents (MME). We also assessed the average pain score during the first week after surgery measured by a numerical pain scale (range, 0–10). Our secondary outcome was the rate of return of unused prescribed opioids at the 6-week postoperative visit utilizing a disposable drug deactivation system.

Results

From April 2019 to September 2021, 152 participants were enrolled: 92 (61%) in the younger cohort (mean age, 51 ± 8 years) and 60 (39%) in the older cohort (mean age, 72 ± 6 years). For our primary outcome, younger women used significantly more opioids during the first postoperative week compared with older women (49 ± 71 vs 28 ± 40 MME, respectively, P = 0.04), despite no difference in average pain scores (4 ± 2 younger vs 3 ± 2 older, P = 0.05). For our secondary outcome, 23% of participants returned their opioids for disposal with the drug deactivation system.

Conclusions

Younger women had higher postoperative opioid use despite similar pain scores after urogynecologic surgery. Among those prescribed opioids, a quarter of participants returned their opioids for disposal at their postoperative visit.
Status Cataplecticus Induced by an Abrupt Duloxetine Withdrawal—A Case Report
Authors: Cierny Marek , Feemster John , Hamid Mohsin , Battistini Humberto A.
Published: July 2023

In persons with narcolepsy type 1, sudden withdrawal of antidepressants can cause status cataplecticus. We describe a 77-year-old female patient with long-standing history of narcolepsy type 1 complaining of recurrent short sudden episodes of whole-body paralysis, with preserved consciousness and memory. Episodes started an hour after her family invited her to celebrate Mother's Day. One week prior, patient had abruptly discontinued duloxetine. Cataplectic episodes resolved within 24 hours after resumption of duloxetine and treatment of hypokalemia. Status cataplecticus has been reported after withdrawal of venlafaxine, fluoxetine, and clomipramine. This is the first report of status cataplecticus due to duloxetine withdrawal. We review the pathophysiology of antidepressant withdrawal-induced status cataplecticus. In persons with narcolepsy type 1, physicians discontinuing any antidepressant should counsel on adverse effects of antidepressant withdrawal and reduce the dose in tapering manner.
Fundamental parameters governing the transmission of conjugative plasmids
Authors: Rodriguez-Grande Jorge , Ortiz Yelina , Garcillan-Barcia M. Pilar , de la Cruz Fernando , Fernandez-Lopez Raul
Published: July 2023

Because their ability to spread infectiously, conjugative plasmids represent a major route for the propagation of antibiotic resistances. In the wild, there are hundreds of different plasmids, but their distribution, prevalence and host range are extremely variable. To understand the reasons behind these ecological differences, we need to obtain precise models for plasmid transmission dynamics. Here, we show that the dynamics of plasmid transmission follow a simple ecological model known as Holling’s Type II Functional Response. Plasmid transmission dynamics can be faithfully captured using two parameters: the searching rate (the pace at which a donor bacterium encounters a suitable recipient) and the handling time (the time required for a donor to transfer the plasmid). By analyzing the dynamics of different plasmid prototypes, we show that these parameters are characteristic of the plasmid transfer machinery. Quantifying the dynamics of plasmid spread may shed light on the epidemiology of antibiotic resistance genes.
Transposable elements regulate thymus development and function
Authors: Larouche Jean-David , Laumont Céline M. , Trofimov Assya , Vincent Krystel , Hesnard Leslie , Brochu Sylvie , Côté Caroline , Humeau Juliette , Bonneil Éric , Lanoix Joël , Durette Chantal , Gendron Patrick , Laverdure Jean-Philippe , Richie Ellen R. , Lemieux Sébastien , Thibault Pierre , Perreault Claude
Published: July 2023

Transposable elements (TE) are repetitive sequences representing ∼45% of the human and mouse genomes and are highly expressed by medullary thymic epithelial cells (mTEC). In this study, we investigated the role of TEs on T-cell development in the thymus. We performed multi-omic analyses of TEs in human and mouse thymic cells to elucidate their role in T cell development. We report that TE expression in the human thymus is high and shows extensive age- and cell lineage-related variations. TE expression correlates with multiple transcription factors in all cell types of the human thymus. Two cell types express particularly broad TE repertoires: mTECs and plasmacytoid dendritic cells (pDC). In mTECs, transcriptomic data suggest that TEs interact with transcription factors essential for mTEC development and function (e.g., PAX1 and REL), and immunopeptidomic data showed that TEs generate MHC-I-associated peptides implicated in thymocyte education. Notably, AIRE, FEZF2, and CHD4 regulate small yet non-redundant sets of TEs in murine mTECs. Human thymic pDCs homogenously express large numbers of TEs that likely form dsRNA, which can activate innate immune receptors, potentially explaining why thymic pDCs constitutively secrete IFN LJ/β. This study highlights the diversity of interactions between TEs and the adaptive immune system. TEs are genetic parasites, and the two thymic cell types most affected by TEs (mTEcs and pDCs) are essential to establishing central T-cell tolerance. Therefore, we propose that orchestrating TE expression in thymic cells is critical to prevent autoimmunity in vertebrates.
A data standard for the reuse and reproducibility of any stable isotope probing-derived nucleic acid sequence (MISIP)
Authors: Simpson Abigayle , Wood Charlson Elisha M. , Smith Montana , Beilsmith Kathleen , Koch Ben , Walls Ramona L. , Wilhelm Roland C.
Published: July 2023

DNA/RNA-stable isotope probing (SIP) is a powerful tool to linkin situmicrobial activity to sequencing data. Every SIP dataset captures distinct information about microbial community metabolism, kinetics, and population dynamics, offering novel insights according to diverse research questions. Data re-use maximizes the information available from the time and resource intensive SIP experimental approach. Yet, a review of publicly available SIP sequencing metadata reveals that critical information necessary for reproducibility and reuse is often missing. Here, we outline the Minimum Information for any Stable Isotope Probing Sequence (MISIP) according to the Minimum Information for any (x) Sequence (MIxS) data standard framework and include examples of MISIP reporting for common SIP approaches. Our objectives are to expand the capacity of MIxS to accommodate SIP-specific metadata and guide SIP users in metadata collection when planning and reporting an experiment. The MISIP standard requires five metadata fields: isotope, isotopolog, isotopolog label and approach, and gradient position, and recommends several fields that represent best practices in acquiring and reporting SIP sequencing data (ex.gradient density and nucleic acid amount). The standard is intended to be used in concert with other MIxS checklists to comprehensively describe the origin of sequence data, such as for marker genes (MISIP-MIMARKS) or metagenomes (MISIP-MIMS), in combination with metadata required by an environmental extension (e.g., soil). The adoption of the proposed data standard will assure the reproducibility and reuse of any sequence derived from a SIP experiment and, by extension, deepen understanding ofin situbiogeochemical processes and microbial ecology.
Association between the rifampicin resistance mutations and rifabutin susceptibility inMycobacterium tuberculosis: a meta-analysis
Authors: Wang Wenli , Zhou Hongjuan , Cai Long , Yang Tingting
Published: July 2023

Some rifampicin-resistantMycobacterium tuberculosis(MTB) strains were susceptible to rifabutin (RFB) and may be amenable to treatment with RFB. We performed a meta-analysis of available cross-sectional studies to determine which RIF-resistance mutations were associated with rifabutin susceptibility. We identified studies through PubMed, Web of Science, Embase, and Cochrane Library up to June 1, 2023. Studies that met our criteria were those that investigatedrpoBmutations and reported phenotypic drug susceptibility for RIF and RFB. The relationship between RIF-resistance mutations to RFB-susceptibility was evaluated using odds ratio (OR). Twenty-five studies comprised 4,333 clinical RIF-resistant MTB isolates from 21 different countries met our criteria for inclusion. Of these isolates, 21.00% (910/4333) were susceptible to RFB. We found seven RIF-resistance mutations were high confidence (OR>10) in predicting RFB-susceptibility, which were D435V, D435Y, D435F, H445L, L430R, S441L, and S441Q. Among strains carrying these mutations, 83.01% (435/524) were susceptible to RFB. The minimum inhibition concentrations (MICs) of these strains revealed that they had low MIC (D435V, D435F, H445L, and D435Y) or were susceptible (S441L) for RFB and exhibited a significant lack of correlation between MICs to RIF and RFB. Mutations such as H445C, H445G, H445N, L430P, and L452P showed a moderate confidence (5<OR≤10) in prediction of RFB-susceptibility. Of these mutants, 62.16% (69/111) were susceptible to RFB. The most common RIF-resistance mutations S450L, as well as S450W, were associated with RFB-resistance (OR<1). These results provide a theoretical basis for molecular detection of RFB-susceptible TB and alternative treatment with RFB in MDR/RR-TB patients.
p53 amyloid pathology with cancer grades and p53 mutations
Authors: Sengupta Shinjinee , Singh Namrata , Paul Ajoy , Datta Debalina , Chatterjee Debdeep , Mukherjee Semanti , Gadhe Laxmikant , Devi Jyoti , Yeshwant M , Jolly Mohit Kumar , Maji Samir K.
Published: July 2023

p53 mutation and amyloid formation are implicated with cancer pathogenesis, but the direct demonstration of the link between p53 amyloid load and cancer progression is lacking. Using multi-disciplinary techniques and a cohort of 59 tumor tissues (53 from Indian cancer patients and six normal tissues) of oral and stomach cancer types, we showed that p53 amyloid load and cancer grades are highly correlated. Further, next-generation sequencing (NGS) data suggest that not only mutant p53 (e.g., SNVs, deletions, and insertions) but wild-type p53 also formed amyloids either in the nucleus (50%) and/or in the cytoplasm in most cancer tissues. Interestingly, in all these cancer tissues, p53 displays a loss of DNA binding and transcriptional activities, which is highly aggravated with the amyloid load and cancer grades. The p53 amyloids also sequester higher amounts of p63/p73 isoforms in higher-grade of tumor tissues. The data suggest p53 misfolding/aggregation and subsequent amyloid formation lead to loss and gain of p53 tumorigenic function, aggravation of which might determine the cancers grades.
Basal expression of immune receptor genes requires low levels of the phytohormone salicylic acid
Authors: van Butselaar Tijmen , Silva Savani , Lapin Dmitry , Bañales Iñigo , Tonn Sebastian , van Schie Chris , Van den Ackerveken Guido
Published: July 2023

The hormone salicylic acid (SA) plays a crucial role in plant immunity by activating responses that arrest pathogen ingress. Since SA accumulation also penalizes growth, the question remains why healthy plants synthesize this hormone. By overexpressing SA-inactivating hydroxylases inArabidopsis thaliana, we reveal that basal SA levels in unchallenged plants are needed for expression of selected immune receptor and signaling genes, thereby enabling early pathogen detection and activation of immunity.
Distinct senescence mechanisms restrain progression of dysplastic nevi
Authors: Lorbeer Franziska K , Rieser Gabrielle , Goel Aditya , Wang Meng , Oh Areum , Yeh Iwei , Bastian Boris C , Hockemeyer Dirk
Published: July 2023

TERT promoter mutations (TPMs) are frequently found in different cancer types, including approximately 70% of sun-exposed skin melanomas. In melanoma, TPMs are among the earliest mutations and can be present during the transition from nevus to melanoma. However, the specific factors that contribute to the selection of TPMs in certain nevi subsets are not well understood. To investigate this, we analyzed a group of dysplastic nevi (DN) by sequencing genes commonly mutated in melanocytic neoplasms. We examined the relationship between the identified mutations, patient age, telomere length, histological features, and the expression of p16. Our findings reveal that TPMs are more prevalent in DN from older patients and are associated with shorter telomeres. Importantly, these TPMs were not found in nevi with BRAF V600E mutations. Conversely, DN with BRAF V600E mutations were observed in younger patients, had longer telomeres, and a higher proportion of p16-positive cells. This suggests that these nevi arrest growth independently of telomere shortening through a mechanism known as oncogene-induced senescence (OIS). These characteristics extend to melanoma sequencing data sets, where melanomas with BRAF V600E mutations were more likely to haveCDKN2Ainactivation, overriding OIS. In contrast, melanomas without BRAF V600E mutations showed a higher frequency of TPMs. Our data imply that TPMs are selected to bypass replicative senescence (RS) in cells that were not arrested by OIS. Overall, our results indicate that a subset of melanocytic neoplasms face constraints from RS, while others encounter OIS and RS. The order in which these barriers are overcome during progression to melanoma depends on the mutational context.
CDK12/CDK13 inhibition disrupts a transcriptional program critical for glioblastoma survival
Authors: Lier Silje , Lund Solveig Osnes , Lipsa Anuja , Frauenknecht Katrin B. M. , Rein Idun Dale , Jain Preeti , Lång Anna Ulrika , Lång Emma Helena , Meyer Niklas , Dutta Aparajita , Anand Santosh , Nesse Gaute Johan , Johansen Rune Forstrøm , Klungland Arne , Rinholm Johanne Egge , Bøe Stig Ove , Anand Ashish , Pollard Steven Michael , Niclou Simone P. , Lerdrup Mads , Pandey Deo Prakash
Published: July 2023

Glioblastoma is the most prevalent and aggressive malignant tumor of the central nervous system. With a median overall survival of only one year, glioblastoma patients have a particularly poor prognosis, highlighting a clear need for novel therapeutic strategies to target this disease. Transcriptional cyclin-dependent kinases (tCDK), which phosphorylate key residues of RNA polymerase II (RNAPII) c-terminal domain (CTD), play a major role in sustaining aberrant transcriptional programs that are key to development and maintenance of cancer cells. Here, we show that either pharmacological inhibition or genetic ablation of the tCDKs, CDK12 and CDK13, markedly reduces both the proliferation and migratory capacity of glioma cells and patient-derived organoids. Using a xenograft mouse model, we demonstrate that CDK12/13 inhibition not only reduces glioma growthin vivo. Mechanistically, inhibition of CDK12/CDK13 leads to a genome-wide abrogation of RNAPII CTD phosphorylation, which in turn disrupts transcription and cell cycle progression in glioma cells. In summary, the results provide proof-of-concept for the potential of CDK12 and CDK13 as therapeutic targets for glioblastoma.

Significance statement

Glioblastoma is a common, aggressive, and invasive type of brain tumor that is usually fatal. The standard treatment for glioblastoma patients is surgical resection, radiotherapy, and chemotherapy with DNA-alkylating agents, and unfortunately current treatments only extend overall survival by a few months. It is therefore critical to identify and target additional biological processes in this disease. Here, we reveal that targeting a specific transcriptional addiction for glioma cells by inhibition of CDK12/CDK13 disrupts glioma-specific transcription and cell cycle progression and has potential to provide a new therapeutic strategy for glioblastoma.
Status and Genetic Diversity ofHipposideros prattiin the Northernmost Part of Its Distribution
Authors: Wang Yanmei , Shang Luwen , Wang Jinhe , Zhao Liming , Bu YanZhen
Published: July 2023

Hipposideros prattiis species of bat distributed in caves from Southeast Asia to the Qinling-Funiu Mountain area in China. To understand the dynamic changes in its distribution and evaluate the current health status of the species, we reviewed 48 caves in the northernmost area of theH. prattidistribution and conducted the first analysis of genetic diversity for the species in the region.H. prattiwas only detected in three caves, the four previously distributed caves and the remaining 41 previously undistributed caves were not observed. An analysis based on microsatellite markers revealed a few key points. 1) The average number of observed alleles (Na) ofH. prattiin the region was 3.94, and the average observed heterozygosity (Ho) was 0.5293. All three populations were in Hardy–Weinberg equilibrium. 2) Intra-population was the predominant genetic variation of theH. prattipopulation. 3)H. prattiin the region experienced a bottleneck effect. We found that the three caves whereH. prattiare currently distributed face varying degrees of human interference and the populations are threatened. Management strategies, including appropriate countermeasures to reduce human interference in caves, are urgently needed.
An online shared decision-making intervention for dementia prevention: A parallel group randomized pilot study
Authors: Ownby Raymond L , Davenport Rosemary
Published: July 2023

OBJECTIVES

The objective of this study was to evaluate the acceptability and efficacy of an online dementia prevention intervention based on a cognitive behavioral shared decision-making model.

DESIGN

This was an unblinded pilot study in which participants were randomly assigned to one of two treatment groups.

SETTING

This study was carried out remotely via telephone, video conferencing and online data collection.

PARTICIPANTS

Persons 50 years of age and older interested in developing more brain healthy lifestyles were recruited.

INTERVENTION

Both groups received 12 weekly sessions on lifestyle factors related to cognitive decline. The treatment as usual (TAU) group received the information and was encouraged to make lifestyle changes. The cognitive behavioral shared decision-making model (CBSDM) group received structured weekly sessions with support for evidence-informed personal goal choices and behavior change strategies.

MEASUREMENTS

Primary outcome measures were the Alzheimer Disease Risk Inventory and the Memory Self-Efficacy and Dementia Knowledge Assessment Scales. Participants reported brain health activities during the first, sixth, and 12thweeks of the study.

RESULTS

The intervention was viewed positively by participants who all said they would participate in it again. Participants in the CBSDM group showed increases in knowledge of dementia risk factors and in exercise. Other outcomes were consistent with moderate to large effect sizes for both groups.

CONCLUSIONS

An online intervention providing psychoeducation and behavior change support was viewed positively by older adults. Results provides preliminary support for the CBSDM intervention’s efficacy in promoting brain health in older adults. (243 words)

Registered at clinicaltrials.gov

NCT04822129
Dental students’ self-efficacy and intention to use clear communication techniques that support individuals with low health literacy
Authors: Maybury Catherine , Horowitz Alice M. , Clough Sharon R. , Green Kerry M. , Wang Min Qi , Kleinman Dushanka V. , Baur Cynthia
Published: July 2023

Objectives

Clear and effective communication is critical to delivering quality dental care to all patients, especially those who have low health literacy. There is limited information about U.S. dental students’ exposure to communication techniques shown to improve patient understanding. Our primary objective was to assess rising fourth-year dental students’ knowledge, understanding, skills, self-efficacy, and behavioral intention to use communication techniques such as speaking slowly, using simple language and practicing the teach-back method. We also inquired about whether their dental curricula provided education about and evaluated them on the communication techniques.

Methods

This 2018 national cross-sectional study used a 34-item online survey to assess fourth-year dental students’ behavioral capability, self-efficacy and behavioral intention related to 17 communication techniques. The survey link was sent to 6,061 students; 242 finished it. Statistical analyses included descriptive statistics; ANOVA to examine associations between demographic variables and behavioral intention; and logistic regression to analyze associations between the predictor variables behavioral capability and self-efficacy and the dependent variable behavioral intention. The level of significance was set at p<0.05 for all analyses.

Results

Over 90 percent of students reported having the knowledge and skills to speak slowly, use simple language and teach-back, but they had lower self-efficacy and intention to use these techniques. They also were less knowledgeable, less confident and had lower intention to use other techniques. Students who reported higher self-efficacy were 9.2 times as likely to report higher behavioral intention to use the techniques than those who reported lower self-efficacy, 95% CI (4.10, 16.96), p<.01.

Conclusions

Our results indicate some dental students need additional education and training to increase their knowledge, skills, self-efficacy and behavioral intention related to plain language communication skills. It is possible that communication concepts are introduced in dental school but are not mastered at a level sufficient to be used in practice.
Evolution of compound eye morphology underlies differences in vision between closely relatedDrosophilaspecies
Authors: Buffry Alexandra D , Currea John P , Franke Franziska A , Palavalli-Nettimi Ravindra , Bodey Andrew J , Rau Christoph , Samadi Nazanin , Gstöhl Stefan J , Schlepütz Christian M , McGregor Alistair P , Sumner-Rooney Lauren , Theobald Jamie , Kittelmann Maike
Published: July 2023

Insects have evolved complex visual systems and display an astonishing range of adaptations for diverse ecological niches. Differences in eye size within and betweenDrosophilaspecies provide the opportunity to study the impact of eye structure on vision. Here we further explored differences inD. mauritianaand its sibling speciesD. simulansand confirmed thatD. mauritianahave rapidly evolved larger eyes as a result of more and wider ommatidia thanD. simulanssince their recent common ancestor. The functional impact of eye size, and specifically ommatidia size, is often only estimated based on the rigid surface morphology of the compound eye. Therefore, we used 3D synchrotron radiation tomography to measure optical parameters in 3D, predict optical capacity, and compare the modelled vision toin vivooptomotor responses. Our optical models predicted higher contrast sensitivity forD. mauritiana, which we verified by presenting sinusoidal gratings to tethered flies in a flight arena. Similarly, we confirmed the higher spatial acuity predicted forDrosophila simulanswith smaller ommatidia and found evidence for higher temporal resolution.
New germline Cas9 promoters show improved performance for homing gene drive
Authors: Du Jie , Chen Weizhe , Jia Xihua , Xu Xuejiao , Yang Emily , Zhou Ruizhi , Zhang Yuqi , Metzloff Matt , Messer Philipp W. , Champer Jackson
Published: July 2023

Gene drive systems could be a viable strategy to prevent pathogen transmission or suppress vector populations by propagating drive alleles with super-Mendelian inheritance. CRISPR-based homing gene drives, perhaps the most powerful gene drive strategy, convert wild type alleles into drive alleles in heterozygotes with the help of Cas9 and gRNA. However, achieving successful outcomes with these drives often requires high performance. Specifically, it is desirable to identify Cas9 promoters that yield high drive conversion rates, minimize the formation rate of resistance alleles in both the germline and the early embryo, and limit somatic Cas9 expression. Thus far, high-performance promoters have only been discovered inAnophelesspecies. InDrosophila, thenanospromoter avoids leaky somatic expression, but at the cost of high embryo resistance from maternally deposited Cas9. To improve drive efficiency, we tested elevenDrosophila melanogastergermline promoters in several configurations. Some of the new promoters achieved higher drive conversion efficiency with minimal embryo resistance, but none could completely avoid somatic expression likenanos. However, such somatic expression often did not carry detectable fitness costs when the promoter-Cas9 elements supported a rescue homing drive targeting a haplolethal gene, suggesting somatic drive conversion. Based on our findings, we selected two Cas9 promoter lines for cage experiments with a 4-gRNA suppression drive. While one promoter exhibited substantial somatic effects, leading to a low drive equilibrium frequency, the other outperformednanos, resulting in the successful suppression of the cage population. Overall, these novel Cas9 promoters hold potential advantages for homing drives inDrosophilaspecies and may also possess valuable homologs in other organisms.
Conservation and divergence of regulatory architecture in nitrate-responsive plant gene circuits
Authors: Bian C , Demirer GS , Oz MT , Cai Y , Witham SS , Mason GA , Di Z , Deligne F , Zhang P , Shen R , Gaudinier A , Brady SM , Patron NJ
Published: July 2023

Nitrogen is an essential element for all life processes in plants. As such, plant roots dynamically respond to nitrogen availability below-ground by executing a signaling and transcriptional cascade resulting in altered plant growth, optimized for nutrient uptake. The NIN-LIKE PROTEIN 7 (NLP7) transcription factor senses nitrogen and along with its closely related paralog NLP6, partially coordinates these transcriptional responses. While post-translational regulation of NLP6/7 is well established, its upstream transcriptional regulation remains understudied in Arabidopsis and other plant species. Here, we dissect a previously identified sub-circuit upstream of NLP6/7 in Arabidopsis and which was predicted to contain multiple multi-node feedforward loops suggestive of an optimized design principle of nitrogen transcriptional regulation. This sub-circuit comprises AUXIN RESPONSE FACTOR 18 (ARF18), ARF9, DEHYDRATION RESPONSE ELEMENT BINDING-PROTEIN 26 (DREB26), A NAC-DOMAIN CONTAINING PROTEIN 32 (ANAC032), NLP6 and NLP7 and their regulation of NITRITE REDUCTASE 1 (NIR1). Conservation and divergence of this circuit and their influence on N-dependent root system architecture are similarly assessed inSolanum lycopersicum. The specific binding sites of these factors within their respective promoters and their putativecis-regulatory architecture are identified. The direct or indirect nature of these interactions are validatedin planta.The resulting models were genetically validated in varying concentrations of available nitrate by measuring the transcriptional output of the network revealing rewiring of nitrogen regulation across distinct plant lineages.

Significance Statement

Nitrogen is a critical nutrient for plant growth and yield. While external N has facilitated modern agriculture, over-application of N-containing fertilizers has drastic ecological and environmental consequences. Here, we experimentally validate a six gene regulatory circuit with extensive feedforward loops identified to act upstream of the criticalNIN-LIKE PROTEIN 6/7transcription factors which regulates a nitrogen metabolic enzyme. Our results indicate conservation and divergence in these circuits between Arabidopsis and tomato despite the similar role of NLP7 in N-dependent changes in root system architecture. The resulting network models complement existing knowledge of NLP7 regulation by providing a framework for targeted transcriptional engineering to increase plant nitrogen use efficiency.
Towards scanning nanostructure X-ray microscopy
Authors: Kovyakh Anton , Banerjee Soham , Liu Chia-Hao , Wright Christopher J. , Li Yuguang C. , Mallouk Thomas E. , Feidenhans'l Robert , Billinge Simon J. L.
Published: July 2023

This article demonstrates spatial mapping of the local and nanoscale structure of thin film objects using spatially resolved pair distribution function (PDF) analysis of synchrotron X-ray diffraction data. This is exemplified in a lab-on-chip combinatorial array of sample spots containing catalytically interesting nanoparticles deposited from liquid precursors using an ink-jet liquid-handling system. A software implementation is presented of the whole protocol, including an approach for automated data acquisition and analysis using the atomic PDF method. The protocol software can handle semi-automated data reduction, normalization and modeling, with user-defined recipes generating a comprehensive collection of metadata and analysis results. By slicing the collection using included functions, it is possible to build images of different contrast features chosen by the user, giving insights into different aspects of the local structure.
Crystal-structure determination and Hirshfeld surface analysis of two new thiophene derivatives: (E)-N-{2-[2-(benzo[b]thiophen-2-yl)ethenyl]-5-fluorophenyl}benzenesulfonamide and (E)-N-{2-[2-(benzo[b]thiophen-2-yl)ethenyl]-5-fluorophenyl}-N-(but-2-yn-1-yl)benzenesulfonamide
Authors: Madhan S. , NizamMohideen M. , Pavunkumar Vinayagam , MohanaKrishnan Arasambattu K.
Published: July 2023

In the title compounds, C22H16FNO2S2 (I) and C26H20FNO2S2 (II), the benzothiophene rings are essentially planar with maximum deviations of 0.009 (1) and 0.001 (1) Å for the carbon and sulfur atom in compounds I and II, respectively. In I, the thiophene ring system is almost orthogonal to the phenyl ring attached to the sulfonyl group, with a dihedral angle of 77.7 (1)°. In compound I, the molecular structure is stabilized by weak C—H...O intramolecular interactions formed by the sulfone oxygen atoms, which generate two S(5) ring motifs. In the crystal of I, N—H...O hydrogen bonds link the molecules into R
2
2(8) rings, which are connected into a C(10) chain via C—H...F hydrogen bonds. Intermolecular C—H...π interactions are also observed. In compound II, the molecules are linked via C—H...O and C—H...F hydrogen bonding, generating infinite C(11) and C(13) chains running parallel to [010].