bluuebunny/crossref_metadata_2025 huggingface dataset:
Genetic Diversity, Evolution, and Diagnosis of Sugarcane Yellow Leaf Virus from 19 Sugarcane-Producing Locations Worldwide
Authors: Rott Philippe , Grinstead Sam , Dallot Sylvie , Foster Zachary S. L. , Daugrois Jean H. , Fernandez Emmanuel , Kaye Claudia J. , Hendrickson Leticia , Hu Xiaojun , Adhikari Bishwo , Malapi Martha , Grünwald Niklaus J. , Roumagnac Philippe , Mollov Dimitre
Published: April 2023

Sugarcane yellow leaf virus (SCYLV), the causal agent of yellow leaf, has been reported in an increasing number of sugarcane-growing locations since its first report in the 1990s in Brazil, Florida, and Hawaii. In this study, the genetic diversity of SCYLV was investigated using the genome coding sequence (5,561 to 5,612 nt) of 109 virus isolates from 19 geographical locations, including 65 new isolates from 16 geographical regions worldwide. These isolates were distributed in three major phylogenetic lineages (BRA, CUB, and REU), except for one isolate from Guatemala. Twenty-two recombination events were identified among the 109 isolates of SCYLV, thus confirming that recombination was a significant driving force in the genetic diversity and evolution of this virus. No temporal signal was found in the genomic sequence dataset, most likely because of the short temporal window of the 109 SCYLV isolates (1998 to 2020). Among 27 primers reported in the literature for the detection of the virus by RT-PCR, none matched 100% with all 109 SCYLV sequences, suggesting that the use of some primer pairs may not result in the detection of all virus isolates. Primers YLS111/YLS462, which were the first primer pair used by numerous research organizations to detect the virus by RT-PCR, failed to detect isolates belonging to the CUB lineage. In contrast, primer pair ScYLVf1/ScYLVr1 efficiently detected isolates of all three lineages. Continuous pursuit of knowledge of SCYLV genetic variability is therefore critical for effective diagnosis of yellow leaf, especially in virus-infected and mainly asymptomatic sugarcane plants.
Kinetochore deterioration concommitant with centromere weakening during aging in mouse oocyte meiosis‐I
Authors: Yin Lin , Mihajlović Aleksandar I. , Yang Gongshe , FitzHarris Greg
Published: April 2023

Age‐related oocyte aneuploidy occurs as a result of chromosome segregation errors in female meiosis‐I and meiosis‐II, and is caused by a progressive age‐related deterioration of the chromosome segregation machinery. Here, we assess the impact of age upon the kinetochore, the multi‐protein structure that forms the link between the chromosome and spindle microtubules. We find that in meiosis‐I the outer kinetochore assembles at germinal vesicle breakdown, but that a substantially smaller outer kinetochore is assembled in oocytes from aged mice. We show this correlates with a weaker centromere in aged oocytes and, using nuclear transfer approaches to generate young‐aged hybrid oocytes, we show that outer kinetochore assembly always mirrors the status of the centromere, regardless of cytoplasmic age. Finally, we show that weaker kinetochores in aged oocytes are associated with thinner microtubule bundles, that are more likely to be mis‐attached. We conclude that progressive loss of the centromere with advancing maternal age underpins a loss of the outer kinetochore in meiosis‐I, which likely contributes to chromosome segregation fallibility in oocytes from older females.
Characterization of serotonin‐5‐HTR1E signaling pathways and its role in cell survival
Authors: Sharma Vinay Kumar , Campbell Kiersten , Yang Xuyu , Dale Ryan , Loh Y. Peng
Published: April 2023

5‐Hydroxytryptamine receptor 1E (5‐HTR1E) is reported to activate cyclic AMP (cAMP) and extracellular‐signal related kinases (ERK) pathways via its ligands and binding partners, but the detailed mechanism underlying the serotonin‐induced 5‐HTR1E signaling is still not known. In the present study, we determined the cellular regulators of ERK and cAMP signaling pathways in response to serotonin‐induced 5‐HTR1E activation in 5‐HTR1E overexpressing HEK293 cells. We found that Pertussis Toxin (PTX) treatment completely reversed the effect of serotonin‐5‐HTR1E mediated signaling on cAMP and ERK pathways, confirming the involvement of a Gαi‐linked cascade. We also observed that Gβγ and Gq were not associated with 5‐HTR1E activation, while blocking protein kinase A (PKA) inhibited ERK signaling only, and had no effect on cAMP. Additionally, serotonin‐stimulated ERK1/2 phosphorylation was similar in 5‐HTR1E overexpressing, β‐arrestin‐deficient HEK293 cells and is solely dependent on G protein signaling. siRNA mediated gene knockdown studies in SH‐SY5Y cells revealed that the inhibition of 5‐HTR1E reduced the expression of cMyc, Cyclin D1, Cyclin E and BCL2 genes which are related to cell cycle regulation and survival. MTT assays showed that 5‐HTR1E knockdown in SHSY‐5Y and U118 cells inhibited cell survival significantly. In addition to the signaling mechanism, we also performed RNA‐seq analysis in 5‐HTR1E overexpressing HEK293 cells and found that 5‐HTR1E can regulate the expression of Receptor activity modifying protein 1 (RAMP1), Nuclear receptor 1 (NR4A1) and other Cyclin genes. These findings indicate that serotonin interaction with 5‐HTR1E receptor simultaneously activates cAMP and ERK pathway in HEK293 cells and its expression is important for cell survival.
Confronting Racism in Nursing
Authors: Kirton Carl A.
Published: April 2023

How nurses can contribute to dismantling racism in meaningful ways
Mitigating Homicide Risk During Pregnancy
Authors: Roush Karen
Published: April 2023

This leading cause of maternal death often involves intimate partners and firearms.
Severe Maternal Morbidity and Postpartum Readmission Through 1 Year
Authors: Druyan Brian , Platner Marissa , Jamieson Denise J. , Boulet Sheree L.
Published: April 2023

OBJECTIVE:

To conduct a cohort study to estimate risk for readmission through 1 year postpartum and the most common readmission diagnoses for individuals with and without severe maternal morbidity (SMM) at delivery.

METHODS:

Using national health care claims data from IBM MarketScan Commercial Research Databases (now known as Merative), we identified all delivery hospitalizations for continuously enrolled individuals 15–49 years of age that occurred between January 1, 2016, and December 31, 2018. Severe maternal morbidity at delivery was identified using diagnosis and procedure codes. Individuals were followed for 365 days after delivery discharge, and cumulative readmission rates were calculated for up to 42 days, up to 90 days, up to 180 days, and up to 365 days. We used multivariable generalized linear models to estimate adjusted relative risks (aRR), adjusted risk differences, and 95% CIs for the association between readmission and SMM at each of the timepoints.

RESULTS:

The study population included 459,872 deliveries; 5,146 (1.1%) individuals had SMM during the delivery hospitalization, and 11,603 (2.5%) were readmitted within 365 days. The cumulative incidence of readmission was higher in individuals with SMM than those without at all timepoints (within 42 days: 3.5% vs 1.2%, aRR 1.44, 95% CI 1.23–1.68; within 90 days: 4.1% vs 1.4%, aRR 1.46, 95% CI 1.26–1.69); within 180 days: 5.0% vs 1.8%, aRR 1.48, 95% CI 1.30–1.69; within 365 days: 6.4% vs 2.5%, aRR 1.44, 95% CI 1.28–1.61). Sepsis and hypertensive disorders were the most common reason for readmission within 42 and 365 days for individuals with SMM (35.2% and 25.8%, respectively).

CONCLUSION:

Severe maternal morbidity at delivery was associated with increased risk for readmission throughout the year after delivery, a finding that underscores the need for heightened awareness of risk for complications beyond the traditional 6-week postpartum period.
Atrial Fibrillation (AFIB) in the ICU: Incidence, Risk Factors, and Outcomes: The International AFIB-ICU Cohort Study*
Authors: Wetterslev Mik , Hylander Møller Morten , Granholm Anders , Hassager Christian , Haase Nicolai , Lange Theis , Myatra Sheila N. , Hästbacka Johanna , Arabi Yaseen M. , Shen Jiawei , Cronhjort Maria , Lindqvist Elin , Aneman Anders , Young Paul J. , Szczeklik Wojciech , Siegemund Martin , Koster Thijs , Aslam Tayyba Naz , Bestle Morten H. , Girkov Mia S. , Kalvit Kushal , Mohanty Rakesh , Mascarenhas Joanne , Pattnaik Manoranjan , Vergis Sara , Haranath Sai Praveen , Shah Mehul , Joshi Ziyokov , Wilkman Erika , Reinikainen Matti , Lehto Pasi , Jalkanen Ville , Pulkkinen Anni , An Youzhong , Wang Guoxing , Huang Lei , Huang Bin , Liu Wei , Gao Hengbo , Dou Lin , Li Shuangling , Yang Wanchun , Tegnell Emily , Knight Agnes , Czuczwar Miroslaw , Czarnik Tomasz , Perner Anders ,   the AFIB-ICU Collaborators
Published: April 2023

OBJECTIVES:

To assess the incidence, risk factors, and outcomes of atrial fibrillation (AF) in the ICU and to describe current practice in the management of AF.

DESIGN:

Multicenter, prospective, inception cohort study.

SETTING:

Forty-four ICUs in 12 countries in four geographical regions.

SUBJECTS:

Adult, acutely admitted ICU patients without a history of persistent/permanent AF or recent cardiac surgery were enrolled; inception periods were from October 2020 to June 2021.

INTERVENTIONS:

None.

MEASUREMENTS AND MAIN RESULTS:

We included 1,423 ICU patients and analyzed 1,415 (99.4%), among whom 221 patients had 539 episodes of AF. Most (59%) episodes were diagnosed with continuous electrocardiogram monitoring. The incidence of AF was 15.6% (95% CI, 13.8–17.6), of which newly developed AF was 13.3% (11.5–15.1). A history of arterial hypertension, paroxysmal AF, sepsis, or high disease severity at ICU admission was associated with AF. Used interventions to manage AF were fluid bolus 19% (95% CI 16–23), magnesium 16% (13–20), potassium 15% (12–19), amiodarone 51% (47–55), beta-1 selective blockers 34% (30–38), calcium channel blockers 4% (2–6), digoxin 16% (12–19), and direct current cardioversion in 4% (2–6). Patients with AF had more ischemic, thromboembolic (13.6% vs 7.9%), and severe bleeding events (5.9% vs 2.1%), and higher mortality (41.2% vs 25.2%) than those without AF. The adjusted cause-specific hazard ratio for 90-day mortality by AF was 1.38 (95% CI, 0.95–1.99).

CONCLUSIONS:

In ICU patients, AF occurred in one of six and was associated with different conditions. AF was associated with worse outcomes while not statistically significantly associated with 90-day mortality in the adjusted analyses. We observed variations in the diagnostic and management strategies for AF.
Epigenetic memory of environmental exposures as a mediator of liver disease
Authors: Hlady Ryan A. , Robertson Keith D.
Published: April 2023

Epigenetic changes are a common feature of human disease, including liver disease and its progression to liver cancer. The most frequent form of liver cancer, HCC, is unusual because most of its causes, or etiologic drivers, are known and are dominated by environmental exposures, including viral infection, alcohol abuse, and overnutrition/metabolic syndrome. The epigenome is a regulatory system overlayed on the genetic material that regulates when, where, and to what extent genes are expressed in developmental, cell type, and disease-associated contexts. Deregulation of the epigenome has emerged as a major player in the pathologic effects of liver disease driving exposures, particularly during their early phases when genetic changes are uncommon. Although it is inherent in the definition of an epigenetic process to be reversible, emerging evidence indicates that epigenetic changes persist after the removal of the exposure and contribute to long-term risk of disease progression. In other systems, environmental exposures lead to beneficial adaptive changes in expression that facilitate processes such as wound healing, and these too are driven by epigenetic changes. What remains unclear, however, is what drives the transition from a beneficial epigenetic memory to a maladaptive scar, the epigenetic processes involved in forming these memories, and whether this process can be modulated for therapeutic purposes. In this review, we discuss these concepts in relation to liver disease and more broadly using examples from other tissue types and diseases, and finally consider how epigenetic therapies could be used to reprogram maladaptive epigenetic memories to delay and/or prevent hepatocarcinogenesis.
Association of Optic Nerve Head and Macular Optical Coherence Tomography Measures With Glaucoma-Related Disability
Authors: Bonham Luke W. , Mihailovic Aleksandra , Xiao Grace , West Sheila K. , Friedman David S. , Ramulu Pradeep Y.
Published: April 2023

Précis:

Optical coherence tomography (OCT) estimated retinal nerve fiber layer (RNFL) thickness associated with glaucoma-related disability independent of the visual field (VF) damage and thus may provide additional patient-relevant disability information beyond what is captured by standard VF testing.

Purpose:

To examine whether OCT metrics [peripapillary RNFL thickness and macular ganglion cell/inner plexiform layer (GCIPL) thickness] are associated with quality of life (QoL) measures and additional disability metrics, and whether these associations are independent of VF damage.

Methods:

In this cross-sectional study, 156 patients with glaucoma or suspected glaucoma received VF testing and OCT scans to measure RNFL and GCIPL thickness. QoL was assessed using the Glaucoma Quality-of-Life 15 and additional disability measures including fear of falling, reading speed, and steps per day were assessed. Multivariable regression models adjusting for relevant covariates tested whether RNFL or GCIPL thickness from the less-impaired eye were associated with disability measures and whether associations were independent of VF damage.

Results:

Greater VF damage is associated with worse QoL (95% CI=0.4–1.4; P<0.001) and slower reading speed (CI=−0.06 to −0.02; P<0.001). Lower RNFL and GCIPL thicknesses were associated with lower QoL scores, but not with QoL scores or other disability metrics after correcting for VF damage. However, post hoc analyses in patients with better eye thicknesses between 55 and 75 µm demonstrated associations between lower RNFL thickness and worse QoL (CI=−2.2 to −0.1; P=0.04) and greater fear of falling (CI=−6.1 to −0.4; P=0.03) even after accounting for VF damage. No such associations were observed for GCIPL thickness.

Conclusions:

OCT RNFL, but not GCIPL, thickness is associated with multiple disability measures independent of VF damage severity.
Malignant Glaucoma Post Gonioscopy-Assisted Transluminal Trabeculectomy
Authors: Mehta Neet , Senthil Sirisha , Warjri Gazella Bruce
Published: April 2023

A 69-year-old male patient with Pseudoexfoliation and open angle glaucoma presented with malignant glaucoma 1 week after undergoing gonioscopy-assisted transluminal trabeculotomy (GATT). This is a rare sight-threatening complication following gonioscopy-assisted transluminal trabeculotomy . A high index of suspicion, early detection, and prompt institution of medical therapy and YAG hyaloidotomy, helped in the resolution of the condition with good intraocular pressure control and visual improvement.
Use of Monoclonal Antibodies in a Pediatric Patient With Severe Combined Immunodeficiency and Persistent SARS-CoV-2 Infection
Authors: Bermejo-Gómez Amanda , Aguilera-Alonso David , Rincón-López Elena María , Catalán-Alonso Pilar , Bardón-Cancho Eduardo J. , García-Morín Marina , Manrique-Rodríguez Silvia , Navarro-Gómez María Luisa
Published: April 2023

We describe the use of monoclonal antibodies for the treatment of persistent SARS-CoV-2 infection in a pediatric patient with severe combined immunodeficiency who required urgent stem cell transplantation to cure his disease.
Clinical and Virologic Impacts of Respiratory Viral Co-infections in Children With Influenza
Authors: Sato Masatoki , Takashita Emi , Katayose Masahiko , Nemoto Kenji , Sakai Nobuko , Fujisaki Seiichiro , Hashimoto Koichi , Hosoya Mitsuaki
Published: April 2023

Background:

Advances in multiplex polymerase chain reaction (PCR) methods have enabled the simultaneous detection of multiple respiratory viruses. We aimed to estimate the clinical and virologic impacts of influenza and other respiratory virus co-infection in children.

Methods:

We enrolled 38 and 35 children diagnosed with influenza and treated with baloxavir marboxil (baloxavir) and oseltamivir, respectively. We performed quantitative reverse transcription-PCR to detect and measure the levels of noninfluenza viruses from 3 nasopharyngeal swab samples collected before and on days 3 and 5 after the initial antiviral dose. We assessed patients’ clinical information using questionnaires.

Results:

One or more respiratory viruses other than influenza virus were detected in 26 (35.6%) of 73 children before antiviral treatment. The influenza virus load and clinical characteristics on the day of influenza onset were similar between children with and without virus co-infections. Of the 26 and 32 children without the emergence of the reduced baloxavir and oseltamivir susceptible variants after treatment, 8 (30.8%) and 7 (21.9%) children were dually co-infected with human rhinovirus only, respectively. The level of human rhinovirus RNA on day 0 in these children was less than −3 log10 that of influenza virus RNA, and the human rhinovirus co-infection had no impact on the disease course either clinically or virologically.

Conclusions:

When multiple respiratory viruses are detected in the same patient, it is necessary to assess clinical symptoms as well as the levels of detected viruses to determine which virus contributes to the development of illness.
Catheter-related Aspergillus Fungemia: Case Report and Literature Review
Authors: Kaur Ishminder , de St Maurice Annabelle
Published: April 2023

Background:

Aspergillus fungemia is encountered infrequently in clinical practice, even in the setting of invasive and disseminated disease. Prolonged Aspergillus fungemia secondary to a central venous catheter is notably rarer.

Methods:

We describe the case of a 13-year-old boy with Aspergillus fungemia in the setting of a central venous catheter who was found to have pulmonary aspergillosis upon evaluation. We reviewed the literature for published cases of catheter-related Aspergillus fungemia and summarized the findings. We also sought to differentiate true fungemia from pseudofungemia and explored the clinical significance of aspergillemia.

Results:

We found 6 published cases of catheter-related Aspergillus fungemia in addition to the 1 discussed in this report. Based on the review of case findings, we propose an algorithm for an approach to a patient with a positive blood culture for Aspergillus spp.

Conclusions:

True aspergillemia is infrequent even in the setting of disseminated aspergillosis among immunocompromised patients and the presence of aspergillemia does not necessarily portend more severe clinical disease course. The management of aspergillemia should involve a determination of the possibility of contamination, and if deemed genuine, a thorough workup to define the extent of the disease process. Treatment durations should be based on tissue sites of involvement and could be shorter in the absence of tissue-invasive disease.
Echocardiography in shock
Authors: Chew Michelle S. , Aissaoui Nadia , Balik Martin
Published: April 2023

Purpose of review

The aim of this study was to illustrate the varying roles of echocardiography in all phases of shock ranging from a rapid, diagnostic tool at the bedside, to a tool for monitoring the adequacy and effects of shock treatment and finally for identification of patients suitable for de-escalation of therapy.

Recent findings

Echocardiography has become an indispensable tool for establishing diagnosis in patients with shock. It is also important for assessing the adequacy of treatment such as fluid resuscitation, vasopressors and inotropes by providing integrated information on cardiac contractility and systemic flow conditions, particularly when used in conjunction with other methods of advanced haemodynamic monitoring. Apart from a traditional, diagnostic role, it may be used as an advanced, albeit intermittent, monitoring tool. Examples include the assessment of heart-lung interactions in mechanically ventilated patients, fluid responsiveness, vasopressor adequacy, preload dependence in ventilator-induced pulmonary oedema and indications for and monitoring during extracorporeal life support. Emerging studies also illustrate the role of echocardiography in de-escalation of shock treatment.

This study provides the reader with a structured review on the uses of echocardiography in all phases of shock treatment.
Which haemodynamic monitoring should we chose for critically ill patients with acute circulatory failure?
Authors: Monnet Xavier , Lai Christopher
Published: April 2023

Purpose of review

To discuss the suitable haemodynamic monitoring for critically ill patients with shock.

Recent findings

For the basic initial monitoring, recent studies emphasized the importance of clinical signs of hypoperfusion and arterial pressure. This basic monitoring is not sufficient in patients resisting to initial treatment. Echocardiography does not allow multidaily measurements and has limitations, for measuring right or left ventricular preload. For a more continuous monitoring, noninvasive and minimally invasive tools are insufficiently reliable, as recently confirmed, and informative. The most invasive techniques, transpulmonary thermodilution and the pulmonary arterial catheter are more suitable. Their effect on outcome is lacking, although recent studies showed their benefit in acute heart failure. For assessing tissue oxygenation, recent publications better defined the meaning of the indices derived from the partial pressure of carbon dioxide. The integration of all data by artificial intelligence is the subject of early research in critical care.

For monitoring critically ill patients with shock, minimally or noninvasive systems are not reliable or informative enough. In the most severe patients, a reasonable monitoring policy can combine continuous monitoring by transpulmonary thermodilution systems or the pulmonary arterial catheter, with an intermittent assessment with ultrasound and measurement of tissue oxygenation.
Exceptional Response of Pancreatic Acinar Cell Carcinoma and Bile Duct Cancer to Platinum-Based Chemotherapy in a Family With a Germline BRCA2 Variant
Authors: Sunami Tomohiko , Yamada Atsushi , Kondo Tomohiro , Kanai Masashi , Nagai Kazuyuki , Uchida Yoichiro , Yokode Masataka , Matsumori Tomoaki , Uza Norimitsu , Murakami Hiromi , Yamada Takahiro , Muto Manabu
Published: April 2023

Pancreatic cancer and its rare subtype, acinar cell carcinoma (PACC), frequently harbor germline and/or somatic variants in homologous recombinant genes, including BRCA2. Individuals possessing germline pathogenic BRCA2 variants are known to have a higher risk of developing various cancers, including breast, ovarian, pancreatic, and bile duct cancers (BDCs). It has been reported that tumors positive for BRCA1/2 variants are sensitive to platinum-based agents. Thus, BRCA1/2 germline testing and comprehensive genomic profiling are recommended to identify genetic susceptibility and to indicate optimal targeted therapy. Here, we report familial occurrence of PACC and BDC associated with BRCA2; both tumors responded exceptionally well to platinum-based chemotherapy. A 37-year-old man was diagnosed with unresectable PACC with a germline BRCA2 variant. He was treated with oxaliplatin-containing chemotherapy and conversion surgery, and remains alive without tumor recurrence after more than 36 months. His father also possessed the identical germline BRCA2 variant and was diagnosed with extrahepatic BDC with lymph node metastases. The tumors showed marked shrinkage upon treatment with cisplatin-containing chemotherapy. Our cases underscore the importance of comprehensive genomic profiling and genetic testing for BRCA2 to ensure optimal therapeutic options for PACC as well as to identify high-risk individuals with various cancers in the family.
New-Onset Diabetes Is a Potential Marker for the Malignant Transformation of Pancreatic Cysts
Authors: Schweber Adam B. , Agarunov Emil , Brooks Christian , Hur Chin , Gonda Tamas A.
Published: April 2023

Objectives

New-onset diabetes mellitus has been shown to be associated with pancreatic cancer (PC) in the general population. Our objective was to leverage real-world data to assess the association of new-onset diabetes (NODM) with malignant transformation in a large longitudinal cohort of pancreatic cyst patients.

Methods

A retrospective longitudinal cohort study was conducted using IBM's MarketScan claims databases from 2009 to 2017. From 200 million database subjects, we selected patients with newly diagnosed cysts without prior pancreatic pathology.

Results

Of the 137,970 patients with a pancreatic cyst, 14,279 had a new diagnosis. Median follow-up was 41.6 months. Patients with NODM progressed to PC at nearly 3 times the rate of patients without a diabetes history (hazard ratio, 2.80; 95% confidence interval, 2.05–3.83) and at a significantly higher rate than patients with preexisting diabetes (hazard ratio, 1.59; 95% confidence interval, 1.14–2.21). The mean interval between NODM and cancer diagnosis was 7.5 months.

Conclusions

Cyst patients who developed NODM progressed to PC at 3 times the rate of nondiabetics and at a greater rate than preexisting diabetics. The diagnosis of NODM preceded cancer detection by several months. These results support the inclusion of diabetes mellitus screening in cyst surveillance algorithms.
Stent-Associated Infectious Complications After Pancreatoduodenectomies Can Be Prevented by Perioperative Antibiotic Therapy
Authors: Biesel Esther A. , Chikhladze Sophia , Ruess Dietrich A. , Hopt Ulrich T. , Fichtner-Feigl Stefan , Wittel Uwe A.
Published: April 2023

Objectives

Perioperative morbidity after pancreatoduodenectomies is still high. One potentially responsible factor is the insertion of bile duct stents before surgery. In our single-center study, we evaluated the influence of preoperative bile duct stenting combined with perioperative antibiotic therapy versus primary surgery in carcinoma patients.

Methods

Clinical data of 973 patients undergoing pancreatoduodenectomy at the University Hospital Freiburg from 2002 to 2018 were explored retrospectively. Postoperative pancreatic fistula, delayed gastric emptying (DGE), and postpancreatectomy hemorrhage (PPH) were graded by current international definitions. Patients with pancreatic ductal adenocarcinoma or periampullary carcinoma were included.

Results

We included 634 patients of whom 372 (58.7%) were treated with preoperative bile duct stenting. No difference concerning postoperative pancreatic fistula was observed (P = 0.479). We found more wound infections (stent 18.4%, no stent 11.1%, P = 0.008) but a significantly lower rate of PPH and DGE in stented patients (PPH 7.5% vs 11.9%, P = 0.044; DGE 16.5% vs 22.5%, P = 0.039). Surprisingly, intra-abdominal abscesses were reduced in stented patients (9.4% vs 15.0%, P = 0.022), just as insufficiencies of the biliodigestive anastomosis (P = 0.021).

Conclusions

Perioperative antibiotic therapy seems to reduce the risk for severe intra-abdominal infectious complications in stent-bearing patients.
Integrated Physiology of the Exocrine and Endocrine Compartments in Pancreatic Diseases
Authors: Mastracci Teresa L. , Apte Minoti , Amundadottir Laufey T. , Alvarsson Alexandra , Artandi Steven , Bellin Melena D. , Bernal-Mizrachi Ernesto , Caicedo Alejandro , Campbell-Thompson Martha , Cruz-Monserrate Zobeida , El Ouaamari Abdelfattah , Gaulton Kyle J. , Geisz Andrea , Goodarzi Mark O. , Hara Manami , Hull-Meichle Rebecca L. , Kleger Alexander , Klein Alison P. , Kopp Janel L. , Kulkarni Rohit N. , Muzumdar Mandar D. , Naren Anjaparavanda P. , Oakes Scott A. , Olesen Søren S. , Phelps Edward A. , Powers Alvin C. , Stabler Cherie L. , Tirkes Temel , Whitcomb David C. , Yadav Dhiraj , Yong Jing , Zaghloul Norann A. , Sander Maike , Pandol Stephen J.
Published: April 2023

The “Integrated Physiology of the Exocrine and Endocrine Compartments in Pancreatic Diseases” Workshop was a 1.5-day scientific conference at the National Institutes of Health (Bethesda, MD) that engaged clinical and basic science investigators interested in diseases of the pancreas. This report summarizes the workshop proceedings. The goal of the workshop was to forge connections and identify gaps in knowledge that could guide future research directions. Presentations were segregated into 6 major themes, including (a) Pancreas Anatomy and Physiology; (b) Diabetes in the Setting of Exocrine Disease; (c) Metabolic Influences on the Exocrine Pancreas; (d) Genetic Drivers of Pancreatic Diseases; (e) Tools for Integrated Pancreatic Analysis; and (f) Implications of Exocrine-Endocrine Crosstalk. For each theme, there were multiple presentations followed by panel discussions on specific topics relevant to each area of research; these are summarized herein. Significantly, the discussions resulted in the identification of research gaps and opportunities for the field to address. In general, it was concluded that as a pancreas research community, we must more thoughtfully integrate our current knowledge of the normal physiology as well as the disease mechanisms that underlie endocrine and exocrine disorders so that there is a better understanding of the interplay between these compartments.
Analysis of Clinical Characteristics and Survival in Patients With Functional Neuroendocrine Tumors of Gastrointestinal Origin
Authors: Kaur Anahat , Wang Shuai , Herbert Joshua , Steinberg Lewis , Kumar Abhishek
Published: April 2023

Objectives

Functional neuroendocrine tumors (FNETs) are characterized by excess secretion of disease-specific hormones. In this study, we attempted to define survival trends in patients with some of these uncommon tumors.

Methods

Using the Surveillance, Epidemiology, and End Results database, 529 patients with FNETs (gastrinoma, insulinoma, glucagonoma, VIPoma, and somatostatinoma) were identified. We analyzed patient and tumor characteristics, overall survival, and cancer-specific survival.

Results

Functional neuroendocrine tumors were found to be more predominant in White patients older than 50 years. Most common FNETs were gastrinoma (56.3%) and insulinoma (23.8%). Most FNETs were found in the pancreas, with the second most common location being the small bowel. Surgery was the primary modality of treatment, used in 55.8% of the cases. Median overall survival was 9.8 years (95% confidence interval [CI], 7.9–11.8) with a median cancer-specific survival of 18.5 years (95% CI, 12.8–24.2). In multivariate analysis, age >50 years (hazard ratio [HR], 2.7; 95% CI, 2.02–3.64), no surgical resection (HR, 1.88; 95% CI, 1.43–2.46), metastasis (HR, 3.0; 95% CI, 2.0–4.5), and poor differentiation were associated with poor survival. Site and histology did not have a significant impact on survival (P = 0.82 and 0.57 respectively).

Conclusions

Our study highlights the most important prognostic factors for gastrointestinal FNETs.
Therapeutic Targets and Prognostic Biomarkers Among CXC Chemokines in Pancreatic Ductal Adenocarcinoma Microenvironment
Authors: Yin Zi , Chen Sheng
Published: April 2023

Objectives

Pancreatic ductal adenocarcinoma (PDAC) is characterized by occult onset, rapid progression, and poor prognosis. CXC chemokines play an important role in tumor microenvironment and development. However, the potential mechanistic values of CXC chemokines as clinical biomarkers and therapeutic targets in PDAC have not been fully clarified.

Methods

The altered expression, interaction network, and clinical data of CXC chemokines in patients with PDAC were analyzed by the data from the Gene Expression Omnibus and the Tumor Cancer Genome Atlas.

Results

CXCL5 transcriptional level was significantly elevated in PDAC tissues. A significant correlation was found between the expression of CXC1/3/5/8 and the pathological stage of PDAC patients. The PDAC patients with low transcriptional levels of CXCL5/9/10/11/17 were associated with a significantly better prognosis. The functions of differentially expressed CXC chemokines are primarily related to the chemokine signaling pathway, cytokine-cytokine receptor interaction, and viral protein interaction with cytokine and cytokine receptor. RELA, NFKB1, and SP1 are key transcription factors for CXC chemokines, and the SRC family of tyrosine kinases, mitogen-activated protein kinases, CDK5, PRKCQ, ROCK1, ITK, IKBKE, JAK3, and NTRK2 are CXC chemokine targets.

Conclusions

The results indicated that CXC chemokines might serve as therapeutic targets and prognostic biomarkers in PDAC.
Diagnostic Categories and Key Features for Pathological Diagnosis of Endoscopic Ultrasound-Guided Fine Needle Aspiration Biopsy Samples of Pancreatic Lesions
Authors: Naito Yoshiki , Notohara Kenji , Omori Yuko , Aishima Shinichi , Itoi Takao , Ohike Nobuyuki , Okabe Yoshinobu , Kojima Motohiro , Tajiri Takuma , Tanaka Mariko , Tsuneki Masayuki , Nakagohri Toshio , Norose Tomoko , Hirabayashi Kenichi , Fukumura Yuki , Mitsuhashi Tomoko , Yamaguchi Hiroshi , Fukushima Noriyoshi , Furukawa Toru
Published: April 2023

Objectives

This study aimed to establish a reliable and reproducible categorized diagnostic classification system with identification of key features to achieve accurate pathological diagnosis of endoscopic ultrasound-guided fine needle aspiration biopsy (EUS-FNAB) samples of pancreatic lesions.

Methods

Twelve pathologists examined virtual whole-slide images of EUS-FNAB samples obtained from 80 patients according to proposed diagnostic categories and key features for diagnosis. Fleiss κ was used to assess the concordance.

Results

A hierarchical diagnostic system consisting of the following 6 diagnostic categories was proposed: inadequate, nonneoplasm, indeterminate, ductal carcinoma, nonductal neoplasm, and unclassified neoplasm. Adopting these categories, the average κ value of participants was 0.677 (substantial agreement). Among these categories, ductal carcinoma and nonductal neoplasm showed high κ values of 0.866 and 0.837, respectively, which indicated the almost perfect agreement. Key features identified for diagnosing ductal carcinoma were necrosis in low-power appearance; structural atypia/abnormalities recognized by irregular glandular contours, including cribriform and nonuniform shapes; cellular atypia, including enlarged nuclei, irregular nuclear contours, and foamy gland changes; and haphazard glandular arrangement and stromal desmoplasia.

Conclusions

The proposed hierarchical diagnostic classification system was proved to be useful for achieving reliable and reproducible diagnosis of EUS-FNAB specimens of pancreatic lesions based on evaluated histological features.
Reconstruction of Thumb Defects using the Second Dorsal Metacarpal Artery Flap with Two Pivot Points
Authors: Zhang Wenlong , Liu Linfeng , Lu Yun , Liu Yingnan , Zhuang Yongqing , Chen Chao
Published: April 2023

Background:

This study aimed to introduce reconstruction of thumb defects using the second dorsal metacarpal artery (DMA) flap with two pivot points.

Methods:

A retrospective study was conducted with 43 patients (group A) underwent thumb reconstruction using the second DMA flap with two pivot points from Jul 2012 to May 2019. For comparison, we reviewed another cohort of 34 patients (group B) undergoing thumb reconstruction using the first DMA flap. Flap sensation and donor site morbidity were assessed.

Results:

In group A, the mean 2PD was 8.7 mm (range, 6 to 12 mm) and 9.7 mm (range, 7 to 12 mm) on the innervated and non-innervated flaps at the final follow-up, with a significant difference (P = 0.012). In group B, the mean 2PD of the flaps was 7.4 mm (range, 6 to 10 mm). By comparison, group B presented better discriminatory sensation than innervated flaps with double pivot points (P = 0.002). Based on the VAS, the mean score of scar pain and cosmetic appearance of the donor site were 0.1 (0 to 3) and 0.4 (0 to 2) in group A, and 0.5 (0 to 3) and 1.0 (0 to 4) in group B. By comparison, group A presented lower incidence of scar pain (P=0.020) and better cosmetic appearance of the donor site (P=0.019).

Conclusions:

The second DMA flap with two pivot points has a long vascular pedicle, which allows the flap to repair thumb defects. It is associated with low donor site morbidity but suboptimal sensory recovery.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, III.
High-Risk Sexual Activities and Condom Use Patterns During Group Sex Among Men Who Have Sex With Men in Melbourne, Australia
Authors: Lew Chen , Fairley Christopher K. , Tran Julien , Phillips Tiffany R. , Maddaford Kate , Chen Marcus Y. , Bradshaw Catriona S. , Chow Eric P. F.
Published: April 2023

Background:

Few studies have examined the types of sexual activities and condom use during group sex among men who have sex with men (MSM). This study aimed to examine sexual activities and condom use during group sex.

Setting:

A cross-sectional survey among MSM attending a sexual health clinic in Melbourne, Australia, between May 2019 and March 2020.

Method:

Participants were asked whether they had engaged in group sex (sex involving more than 2 participants) within the past 3 months, the number of people involved, the sexual activities they engaged in, and their condom use during the most recent group sex.

Results:

More than a quarter (26.8%, 287 of 1071) had engaged in group sex in the past 3 months, and the median number of people involved was 3 (interquartile range 3–4), including the participant. Fellatio was the most common activity in group sex (94.4%, 271 of 287), followed by kissing (85.7%, 246 of 287) and anal sex (79.8%, 229 of 287). The proportion of men who always used condoms and changed condoms between partners was 27.0% (48 of 178) for insertive and 32.3% (52 of 161) for receptive anal sex. Compared with men not taking pre-exposure prophylaxis (PrEP), men living with HIV (adjusted odds ratio [aOR]: 2.35; 95% confidence interval [CI]: 1.20 to 4.59) and men taking PrEP (aOR: 3.07; 95% CI: 2.21 to 4.26) had higher odds of engaging in group sex after adjusting for confounders.

Conclusion:

Two-thirds of MSM either did not use condoms or did not change condoms between partners during group sex, which may increase sexually transmitted infection transmission between partners.
Hybrid Autologous Costal Cartilage Grafting for Augmentation Rhinoplasty in Asian Patients
Authors: Fu Xiujun , Yin Chuang , Liang Yimin , Zhou Renpeng , Wang Danru , Wang Chen
Published: April 2023

Background:

Autologous costal cartilage has been used for augmentation rhinoplasty in Asia for many years. This study aimed to assess the effectiveness and safety of hybrid grafting of costal cartilage for dorsal augmentation, septal reconstruction, and tip augmentation for Asian patients.

Methods:

A surgical technique was introduced and patients having rhinoplasty using this technique from April 2020 to March 2021 were retrospectively studied. In this technique, costal cartilage was meticulously carved or diced and grafted in various ways mainly based on the anatomic characteristics of nasal skin and subcutaneous soft tissues as well as bone and cartilage framework. The surgical outcomes, patient satisfaction, and complications retrieved from the documented medical records were reviewed and analyzed.

Results:

Twenty-five patients having rhinoplasty with the proposed technique were followed up from 6 months to 12 months. As for cosmetic outcomes, 21 patients were graded as good, 3 patients were graded as fair, and only 1 patient was graded as poor. Those patients who were not graded as good had over-rotated tips, insufficient dorsal augmentation, or asymmetry of nostrils and soft tissue contracture. The overall patient satisfaction was as high as 96.0%. Local infection occurred in 1 patient and hematoma was not observed. Warping and visibility of costal cartilage were not observed in any patients. Slight displacement of diced cartilages was found in 2 patients near the radix 1 week postoperatively.

Conclusions:

Hybrid autologous costal cartilage grafts can be used for both tip refinement and dorsal augmentation for East Asian patients and achieve an outcome of a natural-looking nose with minimal complications.

Level of Evidence:

Level IV.
Microglia at the scene of the crime: what their transcriptomics reveal about brain health
Authors: Arutyunov Artem , Klein Robyn S.
Published: April 2023

Purpose of review

Microglia, which arise from primitive myeloid precursors that enter the central nervous system (CNS) during early development, are the first responders to any perturbance of homeostasis. Although their activation has become synonymous with neurologic disease, it remains unclear whether microglial responses are the cause of or response to neuropathology. Here, we review new insights in the roles of microglia during CNS health and disease, including preclinical studies that transcriptionally profile microglia to define their functional states.

Recent findings

Converging evidence suggests that innate immune activation of microglia is associated with overlapping alterations in their gene expression profiles regardless of the trigger. Thus, recent studies examining neuroprotective microglial responses during infections and aging mirror those observed during chronic neurologic diseases, including neurodegeneration and stroke. Many of these insights derive from studies of microglial transcriptomes and function in preclinical models, some of which have been validated in human samples. During immune activation, microglia dismantle their homeostatic functions and transition into subsets capable of antigen presentation, phagocytosis of debris, and management of lipid homeostasis. These subsets can be identified during both normal and aberrant microglial responses, the latter of which may persist long-term. The loss of neuroprotective microglia, which maintain a variety of essential CNS functions, may therefore, in part, underlie the development of neurodegenerative diseases.

Microglia exhibit a high level of plasticity, transforming into numerous subsets as they respond to innate immune triggers. Chronic loss of microglial homeostatic functions may underlie the development of diseases with pathological forgetting.
Nitrite reductase activity in F420-dependent sulphite reductase (Fsr) from Methanocaldococcus jannaschii
Authors: Heryakusuma Christian , Johnson Eric F. , Purwantini Endang , Mukhopadhyay Biswarup
Published: April 2023

Methanocaldococcus jannaschii

(Mj), a hyperthermophilic and evolutionarily deeply rooted methanogenic archaeon from a deep-sea hydrothermal vent, produces F420-dependent sulphite reductase (Fsr) in response to exposure to sulphite. This enzyme allows Mj to detoxify sulphite, a potent inhibitor of methyl coenzyme-M reductase (Mcr), by reducing it to sulphide with reduced coenzyme F420 (F420H2) as an electron donor; Mcr is essential for energy production for a methanogen. Fsr allows Mj to utilize sulphite as a sulphur source. Nitrite is another potent inhibitor of Mcr and is toxic to methanogens. It is reduced by most sulphite reductases. In this study, we report that MjFsr reduced nitrite to ammonia with F420H2 with physiologically relevant K
m values (nitrite, 8.9 µM; F420H2, 9.7 µM). The enzyme also reduced hydroxylamine with a K
m value of 112.4 µM, indicating that it was an intermediate in the reduction of nitrite to ammonia. These results open the possibility that Mj could use nitrite as a nitrogen source if it is provided at a low concentration of the type that occurs in its habitat.
Phenotypic detection and antimicrobial susceptibility of Burkholderia pseudomallei and other Gram-negative bacteria from clinical specimen on Ashdown agar in Nigeria
Authors: Orababa Oluwatosin Qawiyy , Adesida Solayide A. , Peters Rebecca F. , AbdulGanniyu Zainab , Olakojo Olawale , Abioye Adefunke
Published: April 2023

Burkholderia is a genus comprising Gram-negative bacteria that are metabolically complex and versatile, thriving in frequently hostile settings. Burkholderia psudomallei, the causative agent of melioidosis, is a prominent member of the genus and a clinical pathogen of tropical and sub-tropical regions. This pathogen is well known for its multidrug resistance nature and possible bioweapon potential. There are currently limited reports of this pathogen from clinical specimens in Nigeria. This study aimed to determine the occurrence of B. pseudomallei in clinical settings and characterize the pathogen using phenotypic means. Two hundred and seventeen (217) clinical samples and twenty-eight (28) Gram-negative clinical isolates were collected and analysed using Ashdown selective agar and monoclonal antibody based-latex agglutination. The species-level identification was achieved using the Analytical profile index (API) 20NE system. The susceptibility of the isolates to nine different antimicrobial agents was determined using the disk diffusion method. Sixty-seven (67) culture-positive isolates were obtained using Ashdown selective agar. Twenty-six isolates were believed to be B. pseudomallei through the monoclonal antibody based-latex agglutination test and API 20NE system subsequently identified 14 isolates as Burkholderia. The predominant Burkholderia species was B. cepacia with isolation rate of 26.9% (7/26). No isolate was distinctively identified as B. pseudomallei but four isolates were highly suspected to be B. pseudomallei with similarity indices ranging from 81.9 – 91.3%. Other bacterial species with definitive identity include Aeromonas sp., Sphingomonas sp. and Pseudomonas aeruginosa. The antibiotic susceptibility results revealed an overall resistance to amoxicillin-clavullanic acid (71.4%), cefepime (33.3%), trimethoprim-sulfamethoxazole (38.1%), piperacillin-tazobactam (33.3%), imipenem (66.7%), doxycycline (57.1%), and ceftazidime (66.7%). The highest intermediate resistance was observed for cefepime and piperacillin-tazobactam with a value 66.7% each while no intermediate-resistance for gentamicin, colistin and imipenem. Our findings, therefore, provide a robust basis for not just supporting present and future decisions for expanding diagnostic capability for Burkholderia, but also for investigating the relevance of the pathogens in clinical situations.
Solitalea agri sp. nov., a new member of the genus Solitalea isolated from rhizospheric soil of a jujube tree
Authors: Huq Md. Amdadul , Lee Sun-Young , Moon BoKyung , Choi Changsun , Moon Sung-Kwon , Akter Shahina
Published: April 2023

A Gram-stain negative, aerobic, rod-shaped and creamy pink-coloured bacterium, designated MAHUQ-68T, was isolated from rhizospheric soil of a jujube tree. Colonies grew at 10–40 °C (optimum, 28 °C), pH 6.0–9.0 (optimum pH, 7.0) and in the presence of 0–1.5 % NaCl (optimum 0–0.5 %). Positive for both catalase and oxidase activity. Strain MAHUQ-68T hydrolysed casein, starch, aesculin and l-tyrosine. Based on the results of phylogenetic analysis using 16S rRNA gene and genome sequences, strain MAHUQ-68T clustered together within the genus

Solitalea

. The closest members were

Solitalea longa

HR-AVT (98.8 % sequence similarity),

Solitalea canadensis

DSM 3403T (96.9 %) and

Solitalea koreensis

R2A36-4T (94.0 %). The genome of strain MAHUQ-68 T was 4 250 173 bp long with 68 scaffolds and 3 570 protein-coding genes. The genomic DNA G+C content of the type strain was 38.0 mol%. The average nucleotide identity and in silico DNA–DNA hybridization values between strain MAHUQ-68T and its closest relatives were 72.0–81.4% and 19.8–24.3 %, respectively. The major cellular fatty acids were iso-C15 : 0 and summed feature 3 (C16 : 1
 ω7c and/or C16 : 1
 ω6c). The main respiratory quinone was menaquinone-7. The polar lipids comprised phosphatidylethanolamine, an unidentified aminolipid and four unidentified lipids. Based on these data, strain MAHUQ-68T represents a novel species in the genus

Solitalea

, for which the name Solitalea agri sp. nov. is proposed. The type strain is MAHUQ-68T (=KACC 22249T=CGMCC 1.19062T).